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Xu K, Yu M, Sun Q, Zhang L, Qian X, Su D, Gong J, Shang J, Lin Y, Li X. Cost-effectiveness of PD-1 inhibitors combined with chemotherapy for first-line treatment of oesophageal squamous cell carcinoma in China: a comprehensive analysis. Ann Med 2025; 57:2482019. [PMID: 40131366 PMCID: PMC11938309 DOI: 10.1080/07853890.2025.2482019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 02/20/2025] [Accepted: 03/06/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Programmed death-1 (PD-1) inhibitors combined with chemotherapy have become a standard first-line treatment for advanced oesophageal squamous cell carcinoma (ESCC). Given the high costs associated with immunotherapy, evaluating the cost-effectiveness of different PD-1 inhibitors in the Chinese healthcare setting is essential for guiding treatment decisions and policy development. METHODS A cost-effectiveness analysis was conducted comparing six PD-1 inhibitors-sintilimab, toripalimab, tislelizumab, camrelizumab, serplulimab, and pembrolizumab-combined with chemotherapy for first-line treatment of advanced ESCC. A partitioned survival model was used to calculate incremental cost-effectiveness ratios (ICERs) from healthcare system perspective, with a willingness-to-pay (WTP) threshold set at $36,598.19 per quality-adjusted life year (QALY). Sensitivity analyses were performed to evaluate the robustness of the results. RESULTS The ICERs for toripalimab, camrelizumab, pembrolizumab, serplulimab, sintilimab, and tislelizumab were $32,356.79/QALY, $48,410.64/QALY, $312,743.54/QALY, $121,200.84/QALY, $29,663.42/QALY, and $35,304.33/QALY, respectively. Sintilimab, toripalimab, and tislelizumab were below the WTP threshold. Among all regimens, the top three in life years (LYs) gained were toripalimab, serplulimab, and tislelizumab. Sensitivity analysis showed that utility values and drug prices were key factors influencing ICERs. Probabilistic analysis indicated that toripalimab, sintilimab, and tislelizumab had the highest probabilities of being cost-effective, at 83.1%, 81.4%, and 70.0%, respectively. CONCLUSION Sintilimab, toripalimab, and tislelizumab are the most cost-effective PD-1 inhibitors when combined with chemotherapy for the first-line treatment of advanced ESCC in China, with ICERs below the WTP threshold. While all six PD-1 inhibitors demonstrated clinical benefits, pembrolizumab and serplulimab were less favourable from a cost-effectiveness standpoint. Sensitivity analysis confirmed that drug prices and utility values are significant determinants of cost-effectiveness.
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Affiliation(s)
- Kai Xu
- Department of Pharmacy, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
- Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Man Yu
- Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Qingli Sun
- Department of Pharmacy, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, Shandong Province, China
| | - Lingli Zhang
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu Province, China
| | - Xiaodan Qian
- Department of Pharmacy, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Dan Su
- Department of Pharmacy, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Jinhong Gong
- Department of Pharmacy, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Jingjing Shang
- Department of Pharmacy, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
| | - Yingtao Lin
- Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu Province, China
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China
- Clinical Medical Research Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, China
| | - Xin Li
- Department of Pharmacy, The Second People’s Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China
- Department of Pharmaceutical Regulatory Science and Pharmacoeconomics, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu Province, China
- Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China
- Department of Health Policy, School of Health Policy and Management, Nanjing Medical University, Nanjing, Jiangsu Province, China
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Sun Y, Wang Q, Jiang Y, He J, Jia D, Luo M, Shen W, Wang Q, Qi Y, Lin Y, Zhang Y, Wang L, Wang L, Chen S, Fan L. Lactobacillus intestinalis facilitates tumor-derived CCL5 to recruit dendritic cell and suppress colorectal tumorigenesis. Gut Microbes 2025; 17:2449111. [PMID: 39773173 PMCID: PMC11730368 DOI: 10.1080/19490976.2024.2449111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 11/11/2024] [Accepted: 12/23/2024] [Indexed: 01/11/2025] Open
Abstract
Gut microbes play a crucial role in regulating the tumor microenvironment (TME) of colorectal cancer (CRC). Nevertheless, the deep mechanism between the microbiota-TME interaction has not been well explored. In this study, we for the first time discovered that Lactobacillus intestinalis (L. intestinalis) effectively suppressed tumor growth both in the AOM/DSS-induced CRC model and the ApcMin/+ spontaneous adenoma model. Our investigation revealed that L. intestinalis increased the infiltration of immune cells, particularly dendritic cells (DC), in the TME. Mechanically, the tumor-derived CCL5 induced by L. intestinalis recruited DC chemotaxis through the NOD1/NF-κB signaling pathway. In clinical samples and datasets, we found positive correlation between L. intestinalis, CCL5 level, and the DC-related genes. Our study provided a new strategy for microbial intervention for CRC and deepened the understanding of the interaction between tumor cells and the immune microenvironment modulated by gut microbes.
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Affiliation(s)
- Yong Sun
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Qiwen Wang
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yao Jiang
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Jiamin He
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Dingjiacheng Jia
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Man Luo
- Department of Nutrition, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Wentao Shen
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Qingyi Wang
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yadong Qi
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yifeng Lin
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Ying Zhang
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
| | - Lan Wang
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Liangjing Wang
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
- Prevention and Treatment Research Center of Senescent Disease, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Shujie Chen
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
- Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Prevention and Treatment Research Center of Senescent Disease, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Lina Fan
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
- Institution of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang Province, China
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Li X, Wen X, Luo Z, Wang X, Zhang Y, Wei J, Tian Y, Ling R, Duan Y. Simultaneous detection of volatile and non-volatile metabolites in urine using UPLC-Q-Exactive Orbitrap-MS and HS-SPME/GC-HRMS: A promising strategy for improving the breast cancer diagnosis accuracy. Talanta 2025; 291:127812. [PMID: 40023122 DOI: 10.1016/j.talanta.2025.127812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 02/16/2025] [Accepted: 02/22/2025] [Indexed: 03/04/2025]
Abstract
Breast cancer (BC) is the primary cause of cancer-related deaths in women. Currently, the discovery of biomarkers primarily relies on single platform, which might overlook other potential biomarkers and lead to inaccurate diagnoses. This study aims to: (1) expand the detection range of biomarkers through multiple analytical techniques, thereby improving the accuracy of BC diagnosis, and (2) analyze the metabolic pathways of the biomarkers to explore the metabolic mechanisms underlying BC. Urine samples from BC patients and healthy controls were analyzed using two techniques: Ultra-high performance liquid chromatography combined with Quadrupole-Exactive-Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap-MS), and headspace solid-phase microextraction combined with gas chromatography-high resolution mass spectrometry (HS-SPME/GC-HRMS). Data from each platform was analyzed independently using both univariate and multivariate statistical approaches to identify candidate biomarkers. Subsequently, a mid-level data fusion approach was applied to integrate the candidate biomarkers identified by each platform. The fused data were used to construct orthogonal partial least squares discriminant analysis (OPLS-DA) models and random forest (RF) models, which were then compared against models based on individual platform. The fused RF and OPLS-DA models demonstrated enhanced diagnostic accuracy compared to the individual model. Integrating GC-HRMS and UPLC-Q-Exactive Orbitrap-MS achieved the best performance, with an AUC value of 0.967, sensitivity of 86.37 %, and specificity of 89.19 %. Metabolic pathway analysis revealed that 10 metabolic pathways exert an impact on BC. Four pathways-pyruvate metabolism, sulfur metabolism, taurine and hypotaurine metabolism, and tyrosine metabolism-were found to be associated with BC in both metabolomics and volatolomics studies, indicating that these pathways play pivotal roles in BC. This study confirmed the potential of merging multi-platforms to enhance the accuracy of BC diagnosis, offering new avenues for understanding the metabolic mechanisms of BC.
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Affiliation(s)
- Xian Li
- College of Biology Pharmacy and Food Engineering, Shangluo University, Shangluo, 726000, PR China; Research Center of Analytical Instrumentation, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an, 710069, PR China
| | - Xinxin Wen
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Xi'an, 710032, PR China
| | - Zewei Luo
- Research Center of Analytical Instrumentation, School of Mechanical Engineering, Sichuan University, Chengdu, 610065, PR China
| | - Xuejun Wang
- College of Biology Pharmacy and Food Engineering, Shangluo University, Shangluo, 726000, PR China
| | - Yilin Zhang
- College of Biology Pharmacy and Food Engineering, Shangluo University, Shangluo, 726000, PR China
| | - Jing Wei
- College of Biology Pharmacy and Food Engineering, Shangluo University, Shangluo, 726000, PR China
| | - Yonghui Tian
- Research Center of Analytical Instrumentation, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an, 710069, PR China
| | - Rui Ling
- Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, Xi'an, 710032, PR China.
| | - Yixiang Duan
- Research Center of Analytical Instrumentation, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an, 710069, PR China.
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Hua W, Li F, Yang P, Lu Z, Liu Y, Zhong B, Shen B. Resveratrol derivative modified Ru(II) complexes: Synthesis, characterization, in vitro and in vivo anticancer study. J Inorg Biochem 2025; 267:112873. [PMID: 40048805 DOI: 10.1016/j.jinorgbio.2025.112873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 02/18/2025] [Accepted: 02/25/2025] [Indexed: 03/15/2025]
Abstract
The diversification of ligands provides more opportunities to adjust the photophysical performance as well as the bio-function of Ru(II) complexes as novel photosensitizers. Herein, a kind of Ru(II) complexes carrying resveratrol derivative, amino-Res, as ligand was designed and synthesized. The representative complex (named Ru4) showed potent anticancer activity under the trigger of 520 nm-light. Lipophilicity and cellular accumulation experiments indicated that Ru4 possessed higher LogPO/W value and cell up-take than Ru1-Ru3 and [Ru(bpy)3]2+. Mechanism study revealed that Ru4 could inhibit cancer cell migration, invasion and cancer stemness. The bio-function of Ru4 was mainly inherited from the amino-Res ligand. The in vivo study demonstrated that Ru4 could inhibit the tumor growth without significant system toxicity.
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Affiliation(s)
- Wuyang Hua
- School of Food Science and Nutrition Engineering, Jilin Agricultural Science and Technology University, 77(th) Han Lin Road, Jilin City 132101, China; Jilin Province Brewing Technology Science and Technology Innovation Center, 77(th) Han Lin Road, Jilin City 132101, China.
| | - Fenglin Li
- School of Food Science and Nutrition Engineering, Jilin Agricultural Science and Technology University, 77(th) Han Lin Road, Jilin City 132101, China; Jilin Province Brewing Technology Science and Technology Innovation Center, 77(th) Han Lin Road, Jilin City 132101, China
| | - Ping Yang
- School of Food Science and Nutrition Engineering, Jilin Agricultural Science and Technology University, 77(th) Han Lin Road, Jilin City 132101, China; Jilin Province Brewing Technology Science and Technology Innovation Center, 77(th) Han Lin Road, Jilin City 132101, China
| | - Zhongkui Lu
- School of Food Science and Nutrition Engineering, Jilin Agricultural Science and Technology University, 77(th) Han Lin Road, Jilin City 132101, China; Jilin Province Brewing Technology Science and Technology Innovation Center, 77(th) Han Lin Road, Jilin City 132101, China
| | - Yanxia Liu
- School of Food Science and Nutrition Engineering, Jilin Agricultural Science and Technology University, 77(th) Han Lin Road, Jilin City 132101, China; Jilin Province Brewing Technology Science and Technology Innovation Center, 77(th) Han Lin Road, Jilin City 132101, China
| | - Bao Zhong
- School of Food Science and Nutrition Engineering, Jilin Agricultural Science and Technology University, 77(th) Han Lin Road, Jilin City 132101, China; Jilin Province Brewing Technology Science and Technology Innovation Center, 77(th) Han Lin Road, Jilin City 132101, China
| | - Baoxing Shen
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, 2(nd) Xue Lin Road, Nanjing 210023, China.
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Zeng Z, Yi Z, Xu B. The biological and technical challenges facing utilizing circulating tumor DNA in non-metastatic breast cancer patients. Cancer Lett 2025; 616:217574. [PMID: 39983895 DOI: 10.1016/j.canlet.2025.217574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 02/13/2025] [Accepted: 02/18/2025] [Indexed: 02/23/2025]
Abstract
Breast cancer is one of the most prevalent cancers and has emerged as a major global challenge. Circulating tumor DNA (ctDNA), a liquid biopsy method, overcomes the accessibility limitations of tissue-based testing and is widely used for monitoring minimal residual disease and molecular relapse, predicting prognosis, evaluating the response of neoadjuvant therapy, and optimizing treatment decisions in non-metastatic breast cancer. However, the application of ctDNA still faces many challenges. Here, we survey the clinical applications of ctDNA in non-metastatic breast cancer and discuss the significant biological and technical challenges of utilizing ctDNA. Importantly, we investigate potential avenues for addressing the challenges. In addition, emerging technologies, including fragmentomics detection, methylation sequencing, and long-read sequencing, have clinical potential and could be a future direction. Proper utilization of machine learning facilitates the identification of meaningful patterns from complex fragment and methylation profiles of ctDNA. There is still a lack of clinical trials focused on the subsets of ctDNA (e.g., circulating mitochondrial DNA), ctDNA-inferred drug-resistant clonal evolution, tumor heterogeneity, and ctDNA-guided clinical decision-making in non-metastatic breast cancer. Due to regional differences in the number of registered clinical trials, it is essential to enhance communication and foster global collaboration to advance the field.
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Affiliation(s)
- Zihang Zeng
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, 430071, Wuhan, China
| | - Zongbi Yi
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, 430071, Wuhan, China.
| | - Binghe Xu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
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Wu M, Huang Q, Zhang L, Liu Y, Zeng M, Xie C. Apo10 and TKTL1 in blood macrophages as potential biomarkers for early diagnosis of operable breast cancer. Breast Cancer Res Treat 2025; 210:337-345. [PMID: 39644404 PMCID: PMC11930865 DOI: 10.1007/s10549-024-07569-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 11/22/2024] [Indexed: 12/09/2024]
Abstract
OBJECTIVE Blood macrophage Apo10 and TKTL1 detection is a novel, noninvasive cancer screening approach, but its relevance in breast cancer remains uncertain. We compared the potential diagnostic value of Apo10 and TKTL1 with commonly used tumor markers in differentiating breast cancer patients. METHODS Physical examination and blood sample data from breast cancer patients who did not receive surgery or chemotherapy (retrospective; breast cancer group) and those with benign breast nodules and completely healthy subjects (prospective; control group) were collected from October 2020 to July 2022 at Sun Yat-sen University. Descriptive statistics and receiver operating characteristic (ROC) curves were generated. The area under the ROC curve (AUROC) was calculated to compare the diagnostic efficiency of Apo10 and TKTL1 with conventional biomarkers (carcinoembryonic antigen [CEA], cancer antigens [CA-125, CA-199, CA-153]) in differentiating breast cancer from healthy breasts and benign breast nodules. RESULTS From October 2020 to July 2022, 153 breast cancer patients (primarily early-stage disease: n = 113 (73.9%) stage I/II) and 153 control participants (benign breast nodules, n = 56; healthy, n = 97) were included in this study. The breast cancer subtypes were mainly invasive ductal carcinoma (92.8%), with a few cases of DCIS (5.9%), infiltrating lobular carcinoma (0.7%), and mucinous carcinoma (0.7%). Notably, Apo10, TKTL1, and Apo10 + TKTL1 (APT) levels were significantly greater in the cancer group than in the control group (P < 0.001), demonstrating high diagnostic value (AUC = 0.901, 0.871, 0.938) that surpassed CA-125, CA-199, CA-153, and CEA. In a subgroup analysis excluding stage III patients, APT-based breast cancer screening was minimally affected, with the AUROC (0.933-0.938) varying by ≤ 1%. CONCLUSION Compared with conventional biomarkers, Apo10, TKTL1, and APT showed superior early-stage breast cancer screening efficacy, potentially emerging as a promising marker for discriminating breast cancer from healthy breasts and nontumoral lesions.
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Affiliation(s)
- Minqing Wu
- Cancer Prevention Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfengdong Road, Yuexiu District, Guangzhou, 510060, Guangdong, China
| | - Qiyu Huang
- Cancer Prevention Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfengdong Road, Yuexiu District, Guangzhou, 510060, Guangdong, China
- School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Lijuan Zhang
- Department of Breast Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfengdong Road, Yuexiu District, Guangzhou, 510060, Guangdong, China
| | - Yuying Liu
- Cancer Prevention Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfengdong Road, Yuexiu District, Guangzhou, 510060, Guangdong, China
| | - Musheng Zeng
- Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfengdong Road, Yuexiu District, Guangzhou, 510060, Guangdong, China.
- Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Guangzhou, 510060, Guangdong, China.
| | - Chuanbo Xie
- Cancer Prevention Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, 651 Dongfengdong Road, Yuexiu District, Guangzhou, 510060, Guangdong, China.
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Liu Y, Yang S, Ma Y, Gong Y, Du B, Wang Y, Yang L. HPV E6/E7 mRNA screening alone can be used as a screening method for cervical cancer in premenopausal women in China: A retrospective study. Int J Gynaecol Obstet 2025; 169:215-223. [PMID: 39584422 DOI: 10.1002/ijgo.16043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Accepted: 11/11/2024] [Indexed: 11/26/2024]
Abstract
BACKGROUND This study aimed to assess the value of a HPV E6/E7 mRNA assay (Aptima® HPV [AHPV]) for primary cervical cancer screening combined with menopausal status. METHODS A total of 16 917 women underwent AHPV testing and had complete histopathological results at the Affiliated Hospital of Jining Medical University China between January 1, 2017 and March 31, 2022. We evaluated the performance of different screening strategies and combined strategies, as well as evaluations of different menopausal states. RESULTS When identifying LSIL+ (includes low- and high-grade squamous intraepithelial lesions and invasive cervical cancer [ICC]), the sensitivity (91.2%) and negative predictive value (NPV; 96.6%) were significantly higher for AHPV than for liquid-based cytology assay (LBC; 33.2% and 84.7% for sensitivity and NPV, respectively). Furthermore, the co-testing strategy (cytology combined with AHPV), when compared with AHPV, achieved a slightly higher sensitivity (93.6% vs. 91.2%, respectively, P < 0.001), a similar specificity (61.3% vs. 62.7%, respectively, P = 0.014), a similar positive predictive value (PPV; 37.5% vs. 37.8%, respectively, P = 0.709) and a similar NPV (97.5% vs. 96.6%, respectively, P = 0.001). Moreover, AHPV (when compared with menopausal women) achieved a higher sensitivity (93.5% vs. 77.7%, respectively, P < 0.001), a higher NPV (97.3% vs. 93.9%, respectively, P < 0.001), a similar PPV (37.8% vs. 37.0%, respectively, P = 0.618) and a slightly lower specificity (60.7% vs. 72.1%, respectively, P < 0.001) in premenopausal women. These results were similar when identifying HSIL+ (includes high-grade squamous intraepithelial lesion and ICC). CONCLUSION The present study suggests that initial screening with HPV E6/E7 mRNA testing rather than combined screening is a suitable candidate for cervical cancer screening in China (especially for premenopausal women) based on economic reasons.
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Affiliation(s)
- Ying Liu
- Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Shirong Yang
- Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Yingying Ma
- Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Yingying Gong
- Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Beibei Du
- Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
| | - Yunfei Wang
- Department of Gynecology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Linqing Yang
- Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China
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Li T, Zhang M, Zhang T, Li S, Kou C, Zhao M, Huang J, Cao W, Jin P. Cyclin-dependent kinase 4/6 inhibitors and cardiotoxic events in breast cancer: A pharmacovigilance study based on the FAERS database. Int J Cancer 2025; 156:1404-1418. [PMID: 39538367 DOI: 10.1002/ijc.35255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 10/25/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024]
Abstract
Recent trials have highlighted the cardiotoxicity of ribociclib, a CDK4/6 inhibitor, particularly its association with QT prolongation. However, studies on the link between CDK4/6 inhibitors and cardiotoxic events show inconsistent results, and the factors influencing these events and related drug interactions remain underexplored. To address these uncertainties, our study utilizes the FDA adverse event reporting system database (Q1 2015 to Q1 2024) to examine the cardiotoxic events of CDK4/6 inhibitors in breast cancer patients. We employed a comprehensive analytical framework, applying disproportionality methods including Bayesian confidence propagation neural network, proportional reporting ratio, and reporting odds ratio. Our findings highlight significant variability in cardiotoxic events among different CDK4/6 inhibitors, with ribociclib (IC: 0.26, 95%CI: 0.18-0.34) exhibiting pronounced cardiotoxicity. Notably, ribociclib was associated with serious cardiotoxic events such as torsade de pointes/QT prolongation (IC: 2.11, 95% CI: 1.90-2.29) and conduction defects (IC: 2.07, 95% CI: 1.87-2.23). For the first time, palbociclib has been identified with positive signals for cardiotoxic events at the preferred terms level, including pulmonary oedema, increased blood pressure, myocardial infarction, and cardiac flutter. Moreover, multivariable logistic regression and Bayesian network analyses reveal that age, geographic location, and the number of concomitant medications significantly influence cardiotoxic events. Our study also highlights significant drug interactions that increase the probability of specific cardiotoxic outcomes, notably with drugs like sertraline, lansoprazole, capecitabine, and torasemide. These findings highlight the need for personalized treatment plans to mitigate cardiotoxic events and improve patient safety.
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Affiliation(s)
- Ting Li
- Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application, Beijing Hospital, Beijing, China
| | - Miaomiao Zhang
- Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application, Beijing Hospital, Beijing, China
| | - Tian Zhang
- Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application, Beijing Hospital, Beijing, China
| | - Shaoqiang Li
- Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China
| | - Chen Kou
- Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application, Beijing Hospital, Beijing, China
| | - Ming Zhao
- Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application, Beijing Hospital, Beijing, China
| | - Jing Huang
- Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application, Beijing Hospital, Beijing, China
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Weihang Cao
- Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application, Beijing Hospital, Beijing, China
- Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China
| | - Pengfei Jin
- Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application, Beijing Hospital, Beijing, China
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9
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Pei W, Li J, Lei S, Nie S, Liu L. Burden of major cancers in China attributable to modifiable risk factors: Predictions from 2012 to 2035. Int J Cancer 2025; 156:1369-1379. [PMID: 39503513 DOI: 10.1002/ijc.35233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 09/23/2024] [Accepted: 10/02/2024] [Indexed: 11/08/2024]
Abstract
The cancer burden continues to escalate in China. This study was designed to quantify the burden of deaths attributable to modifiable risk factors for major cancers in China from 2012 to 2035, and to provide evidence-based recommendations for cancer management. Using nationally representative data on risk factors and cancer mortality, a comparative risk assessment approach was employed to calculate the temporal trend of population-attributable fractions (PAFs) for 15 modifiable risk factors associated with major cancers in China. The PAF for modifiable risk factors decreased from 64.5% (95% uncertainty interval [UI]: 46.2%-75.3%) in 2012 to 59.3% (95% UI: 40.6%-71.2%) in 2035. Attributable deaths increased from 1,309,990 (95% UI: 938,217-1,529,170) in 2012 to 1,313,418 (95% UI: 898,411-1,577,189) in 2035, while attributable disability-adjusted life years (DALYs) rose from 28,488,120 (95% UI: 20,471,859-33,308,237) to 33,017,705 (95% UI: 22,730,814-39,564,735). Between 2012 and 2035, the top three risk factors contributing to cancer burden shifted from smoking, insufficient fruit intake and particulate matter <2.5 μm in diameter (PM2.5) exposure to smoking, physical inactivity, and inadequate fruit intake. Controlling modifiable risk factors at recommended levels by 2020 could have prevented around 890,000 deaths and 2.2 million DALYs by 2035. The proportion of cancer burden due to modifiable risk factors is projected to decrease, but the absolute number continues to rise. Adhering to an optimal lifestyle could prevent ~40% of cancer deaths by 2035. Key modifiable risk factors including smoking, physical inactivity, and insufficient intake of fruits require high attention.
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Affiliation(s)
- Wei Pei
- Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Jia Li
- Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Shengxi Lei
- Wuhan Britain-China School, Wuhan, People's Republic of China
| | - Shaofa Nie
- Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Li Liu
- Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
- Hubei Provincial Clinical Research Center for Colorectal Cancer, Wuhan, People's Republic of China
- Wuhan Clinical Research Center for Colorectal Cancer, Wuhan, People's Republic of China
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10
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Wu Y, Li Y, Wang X, Zhou X, Yan X, Wang H, Zhu J, Chen W, Shi J. Disability-adjusted life years for colorectal cancer in China, 2017-2030: A prevalence-based analysis focusing on the impact of screening coverage and the application of local weights. Chin Med J (Engl) 2025:00029330-990000000-01493. [PMID: 40143427 DOI: 10.1097/cm9.0000000000003457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Most studies have evaluated disability-adjusted life years (DALYs) of colorectal cancer (CRC) patients based on a set of generic disability weights (DWs). This study aimed to apply local CRC-stage-specific DWs to estimate the burden of DALYs for CRC (CRC-DALYs) in populations in China and consider the influence of local screening coverage of CRC. METHODS A prevalence-based model was constructed using data from various sources. Years lived with disability (YLDs) were estimated mainly via cumulative prevalence data (based on CRC incidence rates, population numbers, and survival rates), stage-specific proportions of CRC, and DWs of the local population. Years of life lost (YLLs) were calculated based on the CRC mortality rates and standard life expectancies. CRC incidence and mortality rates for the years 2020, 2025, and 2030 were estimated by joinpoint regression, and the corresponding DALYs were predicted. The main assumption was made for CRC screening coverage. Sensitivity analysis was used to assess the impact of population, DWs, and coverage. RESULTS In 2017, among the Chinese population, the estimated number of CRC-DALYs was 4,303,314 (11.8% for YLDs). If CRC screening coverage rate in China (2.3%) remains unchanged, the overall DALYs in 2030 are predicted to increase by 37.2% (45.1% of those aged ≥65 years). More optimistically, the DALYs would then decrease by 0.7% in 2030 (from 5,902,454 to 5,860,200) if the coverage could be increased to 25.0%. A sensitivity analysis revealed that using local DWs would change the base-case values by 5.7%. CONCLUSIONS The estimated CRC-DALYs in China using population-specific DWs were considerably lower (with a higher percentage of YLDs) than the global burden of disease (GBD) estimates (5,865,004, of 4.6% for YLDs), suggesting the impact extent of applying local parameters. Sustainable scale-up CRC screening needs to be in place to moderate the growth trend of CRC-DALYs in China.
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Affiliation(s)
- Yujie Wu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yanjie Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xin Wang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xinyi Zhou
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xinxin Yan
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hong Wang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Department of Cancer Epidemiology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan 450008, China
| | - Juan Zhu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Department of Cancer Prevention, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China
| | - Wanqing Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jufang Shi
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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11
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Li X, Bao J, Ma J. Cost-effectiveness analysis of FOLFOXIRI/FOLFOXIRI and mFOLFOX6/FOLFIRI treatment in first-line and second-line chemotherapy for metastatic colorectal cancer. BMJ Open 2025; 15:e086372. [PMID: 40132845 PMCID: PMC11934415 DOI: 10.1136/bmjopen-2024-086372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 02/28/2025] [Indexed: 03/27/2025] Open
Abstract
OBJECTIVES The aim of this study was to evaluate the cost-effectiveness of FOLFOXIRI/FOLFOXIRI compared with mFOLFOX6/FOLFIRI in first-line and second-line chemotherapy for metastatic colorectal cancer (mCRC) from the perspectives of the USA and China, respectively, and provide a decision-making basis for clinical selection of these two regimens. DESIGN The study used a decision-analytic Markov model to simulate the process of mCRC, including three distinct health states: progression-free survival, progressive disease and death. Clinical data were derived from the TRIBE2 trial.Costs and utilities were obtained from local public databases and literature. One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters' uncertainty in this study. PARTICIPANTS The main included patients were histologically confirmed colorectal adenocarcinoma. INTERVENTIONS First-line and second-line treatment with either FOLFOXIRI/FOLFOXIRI or mFOLFOX6/FOLFIRI. MAIN OUTCOME MEASURES Costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon as primary outcomes. RESULTS Patients treated with the FOLFOXIRI/FOLFOXIRI regimen produced 0.08 QALYs in the USA while 0.04 QALYs in China compared with the mFOLFOX6/FOLFIRI regimen. The final ICERs for FOLFOXIRI/FOLFOXIRI were US$5127.70 per QALY and US$30 478.33 per QALY in the USA and China, which are below the willingness-to-pay (WTP) thresholds. In the USA, when the WTP was US$100 000 for each QALY gained, the probability was nearly 99.6% that the FOLFOXIRI/FOLFOXIRI treatment was cost-effective. In China, when the WTP was US$36 053.01 (3 × GDP) for each QALY gained, the probability was nearly 54.7% that FOLFOXIRI/FOLFOXIRI treatment was cost-effective. CONCLUSION Patients with mCRC treated with FOLFOXIRI/FOLFOXIRI as first-line and second-line chemotherapy may improve health outcomes and expend financial resources more efficiently than mFOLFOX6/FOLFIRI whether in China or the USA, which benefits not only individual survival but also the health care system from a value perspective.
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Affiliation(s)
- Xianglian Li
- The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jianan Bao
- The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Jingjing Ma
- The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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Chen JN, Wang L, He YX, Sun XW, Cheng LJ, Li YN, Yoshida S, Shen ZY. SEL1L-mediated endoplasmic reticulum associated degradation inhibition suppresses proliferation and migration in Huh7 hepatocellular carcinoma cells. World J Gastroenterol 2025; 31:103133. [PMID: 40093667 PMCID: PMC11886529 DOI: 10.3748/wjg.v31.i10.103133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 01/04/2025] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Proteins play a central role in regulating biological functions, and various pathways regulate their synthesis and secretion. Endoplasmic reticulum-associated protein degradation (ERAD) is crucial for monitoring protein synthesis and processing unfolded or misfolded proteins in actively growing tumor cells. However, the role of the multiple ERAD complexes in liver cancer remains unclear. AIM To elucidate the effects of SEL1L-mediated ERAD on Huh7 and explore the underlying mechanisms in vivo and in vitro. METHODS Huh7 cells were treated with ERAD inhibitor to identify ERAD's role. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine and colony formation experiments were performed. Apoptosis level and migration ability were assessed using fluorescence activated cell sorting and Transwell assay, respectively. Huh7 SEL1L knockout cell line was established via clustered regularly interspaced short palindromic repeats, proliferation, apoptosis, and migration were assessed through previous experiments. The role of SEL1L in vivo and the downstream target of SEL1L were identified using Xenograft and mass spectrometry, respectively. RESULTS The ERAD inhibitor suppressed cell proliferation and migration and promoted apoptosis. SEL1L-HRD1 significantly influenced Huh7 cell growth. SEL1L knockout suppressed tumor cell proliferation and migration and enhanced apoptosis. Mass spectrometry revealed EXT2 is a primary substrate of ERAD. SEL1L knockout significantly increased the protein expression of EXT2. Furthermore, EXT2 knockdown partially restored the effect of SEL1L knockout. CONCLUSION ERAD inhibition suppressed the proliferation and migration of Huh7 and promoted its apoptosis. EXT2 plays an important role and ERAD might be a potential treatment for Huh7 hepatocellular carcinoma.
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Affiliation(s)
- Jia-Nan Chen
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of Organ Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
| | - Li Wang
- State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, China
| | - Yu-Xin He
- State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, China
| | - Xiao-Wei Sun
- State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, China
| | - Long-Jiao Cheng
- State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, China
| | - Ya-Nan Li
- State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, China
| | - Sei Yoshida
- State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300071, China
- Research Institute of Transplant Medicine, Nankai University, Tianjin 300192, China
- Nankai International Advanced Research Institute, Shenzhen 518045, Guangdong Province, China
| | - Zhong-Yang Shen
- School of Medicine, Nankai University, Tianjin 300071, China
- Department of Organ Transplant, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
- Research Institute of Transplant Medicine, Nankai University, Tianjin 300192, China
- Tianjin Key Laboratory for Organ Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China
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13
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Ding H, Ke Z, Xiao X, Xin B, Xiong H, Lu W. A Predictive Model Using Six Genes DNA Methylation Markers to Identify Individuals With High Risks of High-Grade Squamous Intraepithelial Lesions and Cervical Cancer. Int J Womens Health 2025; 17:739-749. [PMID: 40123757 PMCID: PMC11928328 DOI: 10.2147/ijwh.s494703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 02/14/2025] [Indexed: 03/25/2025] Open
Abstract
Background Cervical cancer is preceded by low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). Human papillomavirus (HPV) test is a sensitive method for cervical cancer screening, but it is less specific compared with cytological examination, leading to overtreatment and reduced patient compliance. Therefore, new detection methods that can improve the accuracy of cervical cancer screening are needed. Methods In the present study, cervical exfoliated cell samples were collected from 228 Chinese individuals, including 114 healthy control individuals, 46 patients with LSIL, 21 patients with HSIL and 47 patients with cervical cancer. The DNA methylation levels of 12 cervical cancer-related genes were detected using quantitative multiplex methylation-specific PCR. All individuals were divided into high- or low-risk groups. Patients with HSIL and cervical cancer were assigned to the high-risk group, whereas healthy controls and patients with LSIL were assigned to the low-risk group. The ability to predict cancer risks was evaluated using ROC curves and a predictive model for cancer risk was constructed by linear regression analysis. Results The methylation levels were significantly higher for all 12 genes in individuals with cervical cancer or HSIL, compared with those in LSIL or normal group. Family with sequence similarity 19 member A4 (FAM19A4), phosphatase and actin regulator 3 (PHACTR3), somatostatin (SST), Zic family member 1 (ZIC1), paired box 1 (PAX1) and zinc finger protein 671 (ZNF671) were used to construct a predictive model for cancer risk prediction, with a specificity of 89.6% and a sensitivity of 95.0%. Conclusion The present study demonstrated the methylation levels of 12 cervical cancer-related genes were higher in Chinese patients with HSIL or cervical cancer. Also, a predictive model was constructed to distinguish cervical cancer or HSCL from individuals with low risk.
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Affiliation(s)
- Hui Ding
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, Shanghai, 200092, People’s Republic of China
- Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Shanghai, 200092, People’s Republic of China
- Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, People’s Republic of China
| | - Zhonghe Ke
- Department of Research and Development, Shanghai Rightongene Biotechnology Co. Ltd, Shanghai, 201403, People’s Republic of China
| | - Xiao Xiao
- Department of Research and Development, Shanghai Rightongene Biotechnology Co. Ltd, Shanghai, 201403, People’s Republic of China
- School of Physics, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of China
| | - Beibei Xin
- Department of Medicine, Shanghai Rightongene Biotechnology Co. Ltd, Shanghai, 201403, People’s Republic of China
| | - Hui Xiong
- General Manager’s Office, Shanghai Rightongene Biotechnology Co. Ltd, Shanghai, 201403, People’s Republic of China
| | - Wen Lu
- Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, Shanghai, 200092, People’s Republic of China
- Department of Gynecology Oncology, Shanghai First Maternity and Infant Hospital, Shanghai, 200092, People’s Republic of China
- School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China
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14
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Gao F, Liu S, Sun Y, Yu C, Zheng L, Sun L, Wang G, Sun Y, Bao Y, Song Z, Yang X, Ke C. Testes-specific protease 50 heightens stem-like properties and improves mitochondrial function in colorectal cancer. Life Sci 2025; 370:123560. [PMID: 40086746 DOI: 10.1016/j.lfs.2025.123560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 02/26/2025] [Accepted: 03/09/2025] [Indexed: 03/16/2025]
Abstract
AIMS The progression of colorectal cancer (CRC) is driven by a small subset of cancer stem-like cells (CSCs), and mitochondrial function is essential for maintaining their stemness. TSP50, a novel identified oncogene, has been found to promote cell proliferation in multiple cancer types. In this study, we detected the regulatory role of TSP50 in regulating CSC-like properties and mitochondrial mass in CRC. MATERIALS AND METHODS First, TSP50 expression and clinical relevance were analyzed via clinical databases and immunohistochemical (IHC). Subsequently, bioinformatic analyses, CRC cell lines, tumorsphere cultures, and mouse xenograft models were utilized to evaluate the relationship between TSP50 and CSC-like properties as well as mitochondrial mass. Finally, immunofluorescence, immunoprecipitation, and Western blotting were performed to dissect the regulatory mechanisms of TSP50, followed by rescue experiments conducted both in vitro and in vivo. KEY FINDINGS TSP50 was overexpressed in CRC tissues, correlating with poor drug response and shorter overall survival (OS). Meanwhile, TSP50 was shown to enhance CSC-like properties in both CRC cells and mouse xenograft models, while concurrently increasing mitochondrial mass and reducing ROS levels, these effects were partially reversed by inhibition of the PI3K/AKT pathway. Mechanistic investigations revealed that TSP50-induced activation of PI3K/AKT signaling is primarily mediated by the enhanced catalytic activity of PI3K p110α subunit. SIGNIFICANCE Collectively, TSP50 drives CRC malignancy by promoting CSC-like properties and enhancing mitochondrial function through PI3K/AKT signaling. These findings identify TSP50 as a potential therapeutic target for eliminating CSC-like cells and improving clinical outcomes in CRC treatment.
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Affiliation(s)
- Feng Gao
- National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, China; China International Joint Research Center for Human Stem Cell Bank, Northeast Normal University, Changchun, Jilin 130024, China
| | - Sichen Liu
- Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Engineering Laboratory for Thyroid Disease Control, Jilin, Changchun 130033, China; Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Yue Sun
- National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, China
| | - Chunlei Yu
- National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, China
| | - Lihua Zheng
- China International Joint Research Center for Human Stem Cell Bank, Northeast Normal University, Changchun, Jilin 130024, China
| | - Luguo Sun
- National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, China
| | - Guannan Wang
- China International Joint Research Center for Human Stem Cell Bank, Northeast Normal University, Changchun, Jilin 130024, China
| | - Ying Sun
- China International Joint Research Center for Human Stem Cell Bank, Northeast Normal University, Changchun, Jilin 130024, China
| | - Yongli Bao
- China International Joint Research Center for Human Stem Cell Bank, Northeast Normal University, Changchun, Jilin 130024, China
| | - Zhenbo Song
- National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, China
| | - Xiaoguang Yang
- National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130117, China.
| | - Chao Ke
- Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China.
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15
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He FQ, Xu R, Zhou D, Zhou X, Chen XD. Disparities in overall survival of gastric cancer patients after radical gastrectomy: an age and rural-urban residence-based cohort study with propensity score matching analysis. Sci Rep 2025; 15:8479. [PMID: 40074844 PMCID: PMC11903829 DOI: 10.1038/s41598-025-93463-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 03/06/2025] [Indexed: 03/14/2025] Open
Abstract
This study estimated overall survival (OS) among gastric cancer patients stratified by age and rural-urban residence after radical gastrectomy. Patients (n = 286) undergoing curative gastrectomy were categorized into four groups based on age (older ≥ 60 years or younger < 60 years) and residence (rural or urban), including rural older (G1), urban older (G2), rural younger (G3) and urban younger (G4) groups. G1 presented with significantly more males, upper stomach cancers and total gastrectomies, while less patients receiving ≥ 4 cycles of adjuvant chemotherapy. The 5-year OS rates were 39.9% for G1, 61.1% for G2, 73.1% for G3, and 71.2% for G4, with a median OS of 47 months in G1 and not reached for other groups. OS was significantly worse in G1 than other groups (P < 0.05). Multivariate Cox regression identified age, type of gastrectomy, adjuvant chemotherapy, perineural invasion, pT category and pN category as independent prognostic factors. After propensity score matching, rural older patients continued to show significantly inferior OS compared to urban older (hazard ratio = 2.269 [1.274-4.042], P = 0.005) and rural younger (hazard ratio = 2.103 [1.116-3.961], P = 0.021) patients. Rural older patients suffered poorer OS after radical gastrectomy, highlighting the need for special attention and comprehensive treatment strategies.
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Affiliation(s)
- Fu-Qian He
- The Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Rui Xu
- Department of Gastric Surgery, Sichuan Clinical Research Centre for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610041, Sichuan, China
| | - Da Zhou
- Department of Gastric Surgery, Sichuan Clinical Research Centre for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610041, Sichuan, China
| | - Xiang Zhou
- Department of Gastric Surgery, Sichuan Clinical Research Centre for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610041, Sichuan, China.
| | - Xiao-Dong Chen
- Department of Gastric Surgery, Sichuan Clinical Research Centre for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Centre, University of Electronic Science and Technology of China, No. 55, Section 4, South Renmin Road, Chengdu, 610041, Sichuan, China.
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16
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Wu B, Cheng Y, Li L, Du Z, Liu Q, Tan X, Li X, Zhao G, Li E. Role of the sulfur-containing amino acid-ROS axis in cancer chemotherapeutic drug resistance. Drug Resist Updat 2025; 81:101238. [PMID: 40107045 DOI: 10.1016/j.drup.2025.101238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 03/10/2025] [Accepted: 03/10/2025] [Indexed: 03/22/2025]
Abstract
Chemotherapeutic drug resistance remains a major barrier to effective cancer treatment. Drug resistance could be driven in part by adaptive redox remodeling of cancer cells. Paradoxically, drug-resistant malignancies exhibit elevated reactive oxygen species (ROS), as well as amplified antioxidant defenses, which enable cancer cell survival under therapeutic stress. Central to this adaptation is glutathione (GSH), the predominant cellular antioxidant, whose synthesis relies on sulfur-containing amino acids (SAAs) - methionine and cysteine. This review delineates the metabolic interplay between methionine and cysteine in the transsulfuration pathway, highlighting their roles as precursors in GSH biosynthesis. We systematically summarize the key enzymes that drive GSH production and their contributions to resistance against platinum-based drugs and other chemotherapeutics. In addition to GSH synthesis, we summarize the roles of GSH antioxidant systems, including glutathione peroxidases (GPXs), peroxiredoxins (PRDXs), and thioredoxins (TRXs), which are critical in chemotherapeutic drug resistance through ROS scavenging. Recent advances reveal that targeting these enzymes, by pharmacologically inhibiting transsulfuration enzymes or disrupting GSH-dependent antioxidant cascades, can sensitize resistant cancer cells to ROS-mediated therapies. These findings not only clarify the mechanistic links between SAA metabolism and redox adaptation but also provide practical approaches to overcome chemotherapeutic drug resistance. By analyzing metabolic and redox vulnerabilities, this review highlights the therapeutic potential to restore chemosensitivity, offering new options in precision oncology medicine.
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Affiliation(s)
- Bingli Wu
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong Province 515041, China; Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China.
| | - Yinwei Cheng
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong Province 515041, China; Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Liyan Li
- Department of Critical Care Medicine, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong Province 518000, China
| | - Zepeng Du
- Department of Central Laboratory, Shantou Central Hospital, Shantou, Guangdong 515041, China
| | - Qianlou Liu
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong Province 515041, China; Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Xinyue Tan
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong Province 515041, China; Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Xin Li
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong Province 515041, China; Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Guozhi Zhao
- Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
| | - Enmin Li
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, Guangdong Province 515041, China; Chaoshan Branch of State Key Laboratory for Esophageal Cancer Prevention and Treatment, Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China.
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Wang X, Zhang Y, Cheng J, Lin L, Hu Y, Wang A, Zhang Y, Wang R, Li Y, Zhang K, Zhang W. Microstructural diffusion MRI for differentiation of breast tumors and prediction of prognostic factors in breast cancer. Front Oncol 2025; 15:1498691. [PMID: 40110196 PMCID: PMC11919649 DOI: 10.3389/fonc.2025.1498691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 01/06/2025] [Indexed: 03/22/2025] Open
Abstract
Purpose This study aims to investigate the feasibility of cellular microstructural mapping by the diffusion MRI (IMPULSED, imaging microstructural parameters using limited spectrally edited diffusion) of breast tumors, and further to evaluate whether the MRI-derived microstructural features is associated with the prognostic factors in breast cancer. Materials and methods This prospective study collected 232 patients with suspected breast tumors from March to August 2023. The IMPULSED MRI scan included acquisitions of diffusion MRI using both pulsed (PGSE) and oscillating (OGSE) gradient spin echo with the oscillating frequencies up to 33 Hz. The OGSE and PGSE data were fitted by the IMPUSLED method using a two-compartment model to estimate mean cell diameter (d mean), intracellular fraction (fin ), extracellular diffusivity (D ex), and cellularity index (f in/d) within breast tumor lesions. The apparent diffusion coefficients (ADCs) were calculated from the conventional diffusion weighted imaging, PGSE, and OGSE (17 Hz and 33 Hz) sequences (ADCDWI, ADCPGSE, ADC17Hz, and ADC33Hz). The independent samples test was used to compare the d mean, fin , Dex , cellularity index, and ADC values between benign and malignant breast tumors, and between breast cancer subgroups with different risk factors. The receiver operating characteristic (ROC) curve was used to access the diagnostic performance. Results 213 patients were finally included and divided into malignant (n=130) and benign (n=83) groups according to the histopathological results. The d mean (15.74 ± 2.68 vs. 14.28 ± 4.65 μm, p<0.001), f in (0.346 ± 0.125 vs. 0.279 ± 0.212, p<0.001) and cellularity index (21.19 ± 39.54 vs. 19.38 ± 14.87 ×10-3 um-1, p<0.005) values of malignant lesions were significantly higher than those of benign lesions, and the D ex (2.119 ± 0.395 vs. 2.378 ± 0.332 um2/ms, p<0.001) and ADCDWI (0.877 ± 0.148 vs. 1.453 ± 0.356 um2/ms, p<0.001) of malignant lesions were significantly lower than those of benign lesions. For differentiation between benign and malignant breast lesions, ADCDWI showed the highest AUC of 0.951 with the sensitivity of 80.49% and specificity of 98.28%. The combination of d mean, f in, D ex, and cellularity for differentiation between benign and malignant breast lesions showed AUC of 0.787 (sensitivity = 70.73%, and specificity = 77.86%), and the combination of IMPULSED-derived parameters with ADCs by PGSE and OGSE further improve the AUC to 0.897 (sensitivity = 81.93%, and specificity = 81.54%). The f in values of HER-2(+) tumors were significantly lower than those of HER-2(-) tumors (0.313 ± 0.100 vs. 0.371 ± 0.137, p=0.015), and the ADCDWI, ADC17Hz and ADC33Hz values of HER-2(+) tumors were significantly higher than those of HER-2(-) tumors (ADCDWI: 0.929 ± 0.115 vs. 0.855 ± 0.197 um2/ms, p=0.023; ADC17Hz: 1.373 ± 0.306 vs. 1.242 ± 0.301 um2/s, p =0.025; ADC33Hz: 2.042 ± 0.545 vs. 1.811 ± 0.392 um2/s, p = 0.008). The f in (0.377 ± 0.136 vs. 0.300 ± 0.917, p=0.001) and cellularity index (27.22 ± 12.02 vs. 21.66 ± 7.76 ×10-3 um-1, p=0.007) values of PR(+) tumors were significantly higher than those of PR(-) tumor. The ADC17Hz values of PR(+) tumors were significantly lower than those of PR(-) tumors(1.227 ± 0.299 vs. 1.404 ± 0.294 um2/s, p =0.002).The ADC17Hz and D ex values of ER(+) tumors were significantly lower than those of ER(-) tumors (ADC17Hz: 1.258 ± 0.313 vs. 1.400 ± 0.273 um2/s, p = 0.029; D ex: 2.070 ± 0.405 vs. 2.281 ± 0.331 um2/ms, p=0.011). For differentiation between ER(+) and ER(-), the ADC17Hz and D ex showed AUCs of 0.643 (sensitivity = 76.67%, and specificity = 47.06%) and 0.646 (sensitivity = 80.0%, and specificity = 45.98%), and the combination of D ex and ADC17Hz showed AUCs of 0.663 (sensitivity =93.33%, specificity = 36.78%). For differentiation of PR(+) and PR(-), the ADC17Hz, f in, and cellularity index showed AUCs of 0.666 (sensitivity = 68.18%, and specificity = 61.97%), 0.697 (sensitivity = 77.27%, and specificity = 60.27%) and 0.661 (sensitivity = 68.18%, and specificity = 61.64%), respectively, and their combination showed AUCs of 0.729 (sensitivity =72.73%, specificity = 65.75%). For differentiation of HER-2(+) and HER-2(-), the ADCDWI, ADC17Hz, and ADC33Hz, and f in showed AUCs of 0.625 (sensitivity = 59.42%, specificity = 63.04%), 0.632 (sensitivity = 43.66%, and specificity = 84.78%), 0.664 (sensitivity = 47.95%, and specificity = 82.67%) and 0.650 (sensitivity = 77.46%, and specificity = 56.52%), respectively, and their combination showed AUCs of 0.693 (sensitivity = 69.57%, specificity = 64.79%) of HER-2(+) and HER-2(-). Conclusion The IMPULSED method demonstrates promise for characterizing cellular microstructural features in breast tumors, which may be helpful for prognostic risk evaluation in breast cancer.
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Affiliation(s)
- Xiaoyan Wang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Zhang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jingliang Cheng
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Liangjie Lin
- Clinical and Technical Support, Philips Healthcare, Beijing, China
| | - Ying Hu
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Anfei Wang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yong Zhang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ruhua Wang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ying Li
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Kun Zhang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wenhua Zhang
- Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Liu L, Wu P, Wang B, Dong J, Zhang C, Liu W, Ying J. Exploring the role of TIGIT in patients with Small Cell Lung Cancer as a novel predictor of prognosis and immunotherapy response. Cancer Immunol Immunother 2025; 74:134. [PMID: 40035834 PMCID: PMC11880484 DOI: 10.1007/s00262-025-03985-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 02/17/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immune checkpoint playing a crucial role in immunosuppression and immune evasion. This study aims to elucidate the expression patterns, characteristics, and possible mechanisms of TIGIT in small cell lung cancer (SCLC). METHODS TIGIT expression was analyzed across various cancers and normal tissues using The Cancer Genome Atlas (TCGA). Transcriptomic data from SCLC patients, sourced from the Gene Expression Omnibus (GEO) and literature, were analyzed to assess TIGIT-related characteristics. Immunohistochemistry (IHC) was used to verify TIGIT expression in post-surgical and advanced SCLC samples, focusing on expression characteristics, prognostic value, and treatment response. RESULTS TIGIT was significantly overexpressed in various tumors, including SCLC (p < 0.05). Higher expression was associated with better overall survival (OS) (p < 0.05). Notably, a significant positive correlation was observed between TIGIT expression and immune-related metagenes, such as HCK, interferon, and LCK (p < 0.05). Immune infiltration analysis revealed a strong positive correlation between TIGIT expression and immune score in multiple cohorts. Additionally, TIGIT expression correlated positively with immune cells, including CD8 T cells, cytotoxic lymphocytes, and B cells (p < 0.05), and multiple immune checkpoints like BTLA, ICOS, and LAG3 (p < 0.05), while it had a significant negative correlation with the TIDE score (p < 0.05). In the validation section, patients with high TIGIT expression showed significantly prolonged disease-free survival (DFS) and OS (p < 0.05), and demonstrated a better response to adjuvant chemotherapy (ACT) and immunotherapy. CONCLUSION TIGIT serves as a biomarker in SCLC, with its high expression indicating favorable prognosis and treatment response. These effects may be due to TIGIT's unique immune landscape and its association with other immune checkpoints.
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Affiliation(s)
- Li Liu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Peng Wu
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Bingzhi Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jiyan Dong
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Chaoqi Zhang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Wenchao Liu
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Jianming Ying
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
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He R, Jie P, Hou W, Long Y, Zhou G, Wu S, Liu W, Lei W, Wen W, Wen Y. Real-time artificial intelligence-assisted detection and segmentation of nasopharyngeal carcinoma using multimodal endoscopic data: a multi-center, prospective study. EClinicalMedicine 2025; 81:103120. [PMID: 40026832 PMCID: PMC11871492 DOI: 10.1016/j.eclinm.2025.103120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 01/16/2025] [Accepted: 01/31/2025] [Indexed: 03/05/2025] Open
Abstract
Background Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China, and often underdiagnosed due to reliance on physician expertise. Artificial intelligence (AI) can enhance diagnostic accuracy and efficiency using large datasets and advanced algorithms. Methods Nasal endoscopy videos with white light imaging (WLI) and narrow-band imaging (NBI) modes from 707 patients treated at one center in China from June 2020 to December 2022 were prospectively collected. A total of 8816 frames were obtained through standardized data procedures. Nasopharyngeal Carcinoma Diagnosis Segmentation Network Framework (NPC-SDNet) was developed and internally tested based on these frames. Two hundred frames were randomly selected to compare the diagnostic performance between NPC-SDNet and rhinologists. Two external testing sets with 2818 images from other hospitals validated the robustness and generalizability of the model. This study was registered at clinicaltrials.gov (NCT04547673). Findings The diagnostic accuracy, precision, recall, and specificity of NPC-SDNet using WLI were 95.0% (95% CI: 94.1%-96.2%), 93.5% (95% CI: 90.2%-95.2%), 97.2% (95% CI: 96.2%-98.3%), and 93.5% (95% CI: 91.7%-94.0%), respectively, and using NBI were 95.8% (95% CI: 94.0%-96,8%), 93.1% (95% CI: 91.0%-95.6%), 96.0% (95% CI: 95.7%-96.8%), and 97.2% (95% CI: 97.1%-97.4%), respectively. Segmentation performance was also robust, with mean Intersection over Union scores of 83.4% (95% CI: 81.8%-85.6%; NBI) and 83.7% (95% CI: 85.1%-90.1%; WLI). In head-to-head comparisons with rhinologists, NPC-SDNet achieved a diagnostic accuracy of 94.0% (95% CI: 91.5%-95.8%) and processed 1000 frames per minute, outperforming clinicians (68.9%-88.2%) across different expertise levels. External validation further supported the reliability of NPC-SDNet, with area under the receiver operating characteristic curve (AUC) values of 0.998 and 0.977 in NBI images, 0.977 and 0.970 in WLI images. Interpretation NPC-SDNet demonstrates excellent real-time diagnostic and segmentation accuracy, offering a promising tool for enhancing the precision of NPC diagnosis. Funding This work was supported by National Key R&D Program of China (2020YFC1316903), the National Natural Science Foundation of China (NSFC) grants (81900918, 82020108009), Natural Science Foundation of Guangdong Province (2022A1515010002), Key-Area Research and Development of Guangdong Province (2023B1111040004, 2020B1111190001), and Key Clinical Technique of Guangzhou (2023P-ZD06).
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Affiliation(s)
- Rui He
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China
- Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, PR China
| | - Pengyu Jie
- The School of Intelligent Engineering, Sun Yat-Sen University-Shenzhen Campus, Shenzhen, 518107, PR China
| | - Weijian Hou
- Department of Otolaryngology Head and Neck Surgery, Kiang Wu Hospital, 999078, Macau, PR China
| | - Yudong Long
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China
- Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, PR China
| | - Guanqun Zhou
- Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, Guangzhou, PR China
| | - Shumei Wu
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China
- Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, PR China
| | - Wanquan Liu
- The School of Intelligent Engineering, Sun Yat-Sen University-Shenzhen Campus, Shenzhen, 518107, PR China
| | - Wenbin Lei
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China
- Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, PR China
| | - Weiping Wen
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China
- Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, PR China
| | - Yihui Wen
- Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, PR China
- Otorhinolaryngology Institute, Sun Yat-sen University, Guangzhou, Guangdong, PR China
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Xiong TY, Liu ZL, Wu HY, Fan YP, Niu YN. Association between maximal urethral length preservation and postoperative continence after robot-assisted radical prostatectomy: a meta-analysis and systematic review. Asian J Androl 2025; 27:225-230. [PMID: 39435843 PMCID: PMC11949459 DOI: 10.4103/aja202481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 08/06/2024] [Indexed: 10/23/2024] Open
Abstract
ABSTRACT Urinary incontinence is a common complication following robot-assisted radical prostatectomy (RARP). Urethral length has been identified as a factor affecting postoperative continence recovery. In this meta-analysis, we examined the association between use of the maximal urethral length preservation (MULP) technique and postoperative urinary continence in patients undergoing RARP. We conducted a comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library up to December 31, 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to synthesize data and calculate the odds ratio (OR) from eligible studies on continence and MULP. Six studies involving 1869 patients met the eligibility criteria. MULP was positively associated with both early continence (1 month after RARP; Z = 3.62, P = 0.003, OR = 3.10, 95% confidence interval [CI]: 1.68-5.73) and late continence (12 months after RARP; Z = 2.34, P = 0.019, OR = 2.10, 95% CI: 1.13-3.90). Oncological outcomes indicated that MULP did not increase the overall positive surgical margin rate or the positive surgical margin status at the prostate apex (both P > 0.05). In conclusion, the use of the MULP technique in RARP significantly improved both early and late postoperative continence outcomes without compromising oncological outcomes.
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Affiliation(s)
- Tian-Yu Xiong
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- Institute of Urology, Beijing Municipal Health Commission, Beijing 100050, China
| | - Zhan-Liang Liu
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- Institute of Urology, Beijing Municipal Health Commission, Beijing 100050, China
| | - Hao-Yu Wu
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- Institute of Urology, Beijing Municipal Health Commission, Beijing 100050, China
| | - Yun-Peng Fan
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- Institute of Urology, Beijing Municipal Health Commission, Beijing 100050, China
| | - Yi-Nong Niu
- Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- Institute of Urology, Beijing Municipal Health Commission, Beijing 100050, China
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Liu JY, Wang SZ, Yuan HQ, Li JL, Xing PY. Patients with non‑small cell lung cancer with the exon 21 L858R mutation: From distinct mechanisms to epidermal growth factor receptor tyrosine kinase inhibitor treatments (Review). Oncol Lett 2025; 29:109. [PMID: 39776649 PMCID: PMC11704875 DOI: 10.3892/ol.2024.14855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 11/01/2024] [Indexed: 01/11/2025] Open
Abstract
The most common oncogenic driver in non-small cell lung cancer (NSCLC) is epidermal growth factor receptor (EGFR) gene mutations, which are more common in Asian (30-50%) than in Caucasian (10-15%) populations. Exon 19 deletion (ex19del) and exon 21 L858R (ex21 L858R) mutations account for ~45 and 40% of all EGFR mutations, respectively. Moreover, EGFR-tyrosine kinase inhibitors (TKIs) may be more effective and improve the quality of life of patients with NSCLC more than chemotherapy regimens. By contrast, patients with the ex21 L858R mutation may have a lower sensitivity and duration of response to EGFR-TKIs as well as a shorter survival compared with those with the ex19del mutation. However, current guidelines classify ex21 L858R and ex19del as the same condition and recommend the same treatment strategy for both. Aiming for precision medicine, the present review introduces and compares different EGFR-TKIs for the ex21 L858R mutation to assess more personalized treatment options for the population with this mutation.
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Affiliation(s)
- Jia-Yu Liu
- Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Shou-Zheng Wang
- Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101125, P.R. China
| | - Han-Qi Yuan
- Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Jun-Ling Li
- Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Pu-Yuan Xing
- Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
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Xiao YX, Chen J, Li ZY, Zou YX, Zhou XH, Zhang W, Li HL, Bischof EY, Xiang YB. Global trends in gallbladder cancer survival: A 30-year analysis of cancer registry data. Heliyon 2025; 11:e42853. [PMID: 40070950 PMCID: PMC11894304 DOI: 10.1016/j.heliyon.2025.e42853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 02/17/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Background Gallbladder cancer has historically been characterized with a poor prognosis. This study aims to describe the global patterns and temporal trends in gallbladder cancer survival using data from cancer registries. Methods We conducted a systematic review by searching six databases-PubMed, Web of Science, EMBASE, SEER, CNKI, and Wanfang-for using of registry-based data published before January 1, 2024. Survival data were carefully extracted and analyzed from the final set of included studies. Results Among the 55 studies included, more than 320,000 people, suggest that survival improvements for gallbladder cancer have stagnated over the past three decades. No significant improvements in 5-year relative survival rates were observed worldwide. After age standardization, the highest 5-year relative survival rate is 30.6 % (Changzhou, China, 2011-2013 and Korea, 2013-2019), while the lowest is 6.0 % (Austria, 1990). The 5-year relative survival rate for gallbladder cancer was generally higher in Asian populations than in other regions. Survival rates were more favorable in younger individuals, with no differences in survival observed between the sexes. Conclusions Over the past 30 years, the prognosis of patients with gallbladder cancer has not improved significantly worldwide. There is an urgent need for new treatments for gallbladder cancer as well as simple and effective screening methods to improve the survival rate of gallbladder cancer.
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Affiliation(s)
- Yu-Xuan Xiao
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Jun Chen
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Zhuo-Ying Li
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Fudan University, Shanghai, 200025, China
| | - Yi-Xin Zou
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Fudan University, Shanghai, 200025, China
| | - Xiao-Hui Zhou
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
| | - Wei Zhang
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Hong-Lan Li
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
| | - Evelyne Y. Bischof
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China
| | - Yong-Bing Xiang
- Department of Epidemiology & State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200032, China
- School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China
- School of Public Health, Fudan University, Shanghai, 200025, China
- Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China
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Zhu S, Yang C, Bai Y, Kang L, Li T, Yang X, Chen S, Li J. Effects of a perioperative support program on reducing psychological distress for family caregivers of patients with early-stage lung cancer: a pilot randomised controlled trial. BMC Nurs 2025; 24:220. [PMID: 40011924 DOI: 10.1186/s12912-025-02857-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 02/17/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND For family caregivers, lung cancer surgery is an episodic and stressful event. Some family caregivers frequently lack the necessary skills for their roles, and they may experience psychological distress, which reduce their own quality of life whilst affecting the health outcomes of patients. However, research on perioperative support programs that focus on caregivers of patients with early-stage lung cancer is limited. Thus, this study aimed to assess the feasibility, acceptability and preliminary efficacy of a perioperative support program for family caregivers of patients with early-stage lung cancer. METHODS A single-blinded, parallel-group, pilot randomised controlled trial was conducted. Seventy family caregivers of patients with stage I or II lung cancer were recruited from March to May 2022 in the thoracic surgery department of a university-affiliated hospital in Changsha, China. The participants were randomised into the intervention group (n = 35) or control group (n = 35). The intervention consisted of four face-to-face intervention sessions during the hospital stay and two weekly telephone follow-up sessions after discharge, which aimed to improve caregivers' perioperative care knowledge and coping skills to reduce psychological distress and caregiver burden and to improve their quality of life. Feasibility was assessed by the rates of recruitment, attrition, time spent on completing the questionnaire and the duration of each session. Acceptability was evaluated using the Client Satisfaction Questionnaire. Preliminary intervention effects were evaluated on primary (psychological distress) and secondary (caregiver burden, quality of life, coping style and social support) outcomes. RESULTS The feasibility of the program was established at a high recruitment rate of 89.7% and a low attrition rate of 10.0%. The participants were highly satisfied with the program. Although the psychological distress was reduced in the intervention group, the results were not statistically significant (P = 0.106, Cohen's d = - 0.28). No significant differences in caregiver burden, active coping, negative coping, social support and quality of life (P > 0.05 for all) were found between the two groups at 4 weeks after the intervention. CONCLUSIONS The perioperative support program may be feasible and acceptable for family caregivers of patients with early-stage lung cancer. The program provides caregivers with coping and communication skill training and psychoeducational strategies to help them face the perioperative challenges of caring for patients with early-stage lung cancer. Based on the promising results of this pilot study, we have conducted a large-scale randomised controlled trial to evaluate the intervention's effectiveness. TRIAL REGISTRATION This study was retrospectively registered at the Chinese Clinical Trial Registry. Registration Date: February 25, 2022. REGISTRATION NUMBER ChiCTR2200056965.
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Affiliation(s)
- Song Zhu
- Department of Nursing, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Kiang Wu Nursing College of Macau, Macau, China
| | - Chen Yang
- School of Nursing, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yang Bai
- School of Nursing, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Lu Kang
- Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinic Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Tong Li
- Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinic Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiufen Yang
- Department of Emergency, Shenzhen People's Hospital, Shenzhen, Guangdong, China
| | - Shihao Chen
- Clinic Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Jina Li
- Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
- Clinic Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China.
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Liang GZ, Li XS, Hu ZH, Xu QJ, Wu F, Wu XL, Lei HK. Development and validation of a nomogram model for predicting overall survival in patients with gastric carcinoma. World J Gastrointest Oncol 2025; 17:95423. [PMID: 39958550 PMCID: PMC11755997 DOI: 10.4251/wjgo.v17.i2.95423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 10/01/2024] [Accepted: 11/06/2024] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND The prevalence and mortality rates of gastric carcinoma are disproportionately elevated in China, with the disease's intricate and varied characteristics further amplifying its health impact. Precise forecasting of overall survival (OS) is of paramount importance for the clinical management of individuals afflicted with this malignancy. AIM To develop and validate a nomogram model that provides precise gastric cancer prevention and treatment guidance and more accurate survival outcome prediction for patients with gastric carcinoma. METHODS Data analysis was conducted on samples collected from hospitalized gastric cancer patients between 2018 and 2020. Least absolute shrinkage and selection operator, univariate, and multivariate Cox regression analyses were employed to identify independent prognostic factors. A nomogram model was developed to predict gastric cancer patient outcomes. The model's predictability and discriminative ability were evaluated via receiver operating characteristic curves. To evaluate the clinical utility of the model, Kaplan-Meier and decision curve analyses were performed. RESULTS A total of ten independent prognostic factors were identified, including body mass index, tumor-node-metastasis (TNM) stage, radiation, chemotherapy, surgery, albumin, globulin, neutrophil count, lactate dehydrogenase, and platelet-to-lymphocyte ratio. The area under the curve (AUC) values for the 1-, 3-, and 5-year survival prediction in the training set were 0.843, 0.850, and 0.821, respectively. The AUC values were 0.864, 0.820, and 0.786 for the 1-, 3-, and 5-year survival prediction in the validation set, respectively. The model exhibited strong discriminative ability, with both the time AUC and time C-index exceeding 0.75. Compared with TNM staging, the model demonstrated superior clinical utility. Ultimately, a nomogram was developed via a web-based interface. CONCLUSION This study established and validated a novel nomogram model for predicting the OS of gastric cancer patients, which demonstrated strong predictive ability. Based on these findings, this model can aid clinicians in implementing personalized interventions for patients with gastric cancer.
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Affiliation(s)
- Guan-Zhong Liang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Xiao-Sheng Li
- Chongqing Cancer Multi-omics Big Data Application Engineering Research Center, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Zu-Hai Hu
- Department of Health Statistics, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Qian-Jie Xu
- Department of Health Statistics, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Fang Wu
- Research Center for Medicine and Social Development, School of Public Health, Chongqing Medical University, Chongqing 400016, China
| | - Xiang-Lin Wu
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China
| | - Hai-Ke Lei
- The Research Center of Big Data, Chongqing University Cancer Hospital, Chongqing 400030, China
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Zeng L, Tang Y, Huang X, Pei W, Liao Y, Liu J. Combined impact of prognostic nutritional index, fibrinogen-to-albumin ratio, and neutrophil-to-lymphocyte ratio on surgical outcomes and prognosis in hepatocellular carcinoma. Am J Cancer Res 2025; 15:439-451. [PMID: 40084351 PMCID: PMC11897630 DOI: 10.62347/rtmf3105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 02/07/2025] [Indexed: 03/16/2025] Open
Abstract
This study evaluated the predictive value of the prognostic nutritional index (PNI), fibrinogen-to-albumin ratio (FAR), and neutrophil-to-lymphocyte ratio (NLR) for overall survival in hepatocellular carcinoma (HCC) patients. A total of 283 HCC cases from Hunan Provincial People's Hospital were included in the analysis, with 45 additional patients as external validation. The relationship between these indices and patient prognosis was further evaluated using the Kaplan-Meier method and Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of these indices for overall survival (OS) and to determine the optimal cutoff values. ROC curve analysis revealed that the area under the curve (AUC) for PNI, FAR, and NLR was 0.723, 0.857, and 0.872, respectively. Multivariate analysis identified hepatitis history, intraoperative blood transfusion, FAR, NLR, and PNI as independent prognostic factors (all P<0.05). The resulting prediction model demonstrated strong performance in both the training (C-index =0.917) and external validation (C-index =0.853) cohorts, with AUCs of 0.889 and 0.931 for 6-month and 1-year prediction in the validation set, respectively. These findings suggest that preoperative levels of peripheral blood PNI, FAR, and NLR are closely associated with the surgical prognosis of HCC patients. The prognostic prediction model developed based on these indices exhibits good predictive efficacy.
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Affiliation(s)
- Liuhaonan Zeng
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Yixun Tang
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Xiaoling Huang
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Wanmin Pei
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Yongqiong Liao
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
| | - Jitong Liu
- Department of Anesthesiology, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital) Changsha 410000, Hunan, China
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Ye T, Shao S, Yao S, Wang R. The relationship between lateral cervical lymph node positivity rate and recurrence after comprehensive treatment in differentiated thyroid carcinoma: a single-center retrospective cohort study from China. Front Oncol 2025; 15:1484002. [PMID: 40027128 PMCID: PMC11868813 DOI: 10.3389/fonc.2025.1484002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 01/28/2025] [Indexed: 03/05/2025] Open
Abstract
Introduction The lateral cervical lymph node positivity rate has been hypothesized to correlate with the recurrence risk in differentiated thyroid carcinoma (DTC) patients. However, the extent of this association within the Chinese population remains understudied. This study seeks to elucidate the potential causal link between the lymph node positivity rate and DTC recurrence. Methods We conducted a retrospective cohort study, examining clinical records of 4,731 DTC patients who received surgical treatment at the First Medical Center of the General Hospital of the Chinese People's Liberation Army from January 2015 to May 2020. The study variables encompassed demographic and clinical characteristics, including sex, age, tumor size, location, laterality, capsular invasion, lymph node metastasis counts, lymph node positivity rates, histological subtypes, Hashimoto's thyroiditis co-occurrence, and the timing of iodine-131 therapy post-surgery. After applying strict inclusion criteria, 1,074 patients were selected for analysis. Recurrence was defined as structural incomplete response (SIR), confirmed by imaging or histological means. The lymph node positivity rate was calculated as the proportion of positive lymph nodes to the total lymph node count. Results Multivariate analysis revealed a nonlinear association between the lateral cervical lymph node positivity rate and post-treatment recurrence, with a significant threshold at 0.5. The recurrence risk was substantially elevated with a positivity rate below this threshold (HR: 27.48, 95% CI: 7.21-104.70, P<0.0001), while no significant association was observed above it (HR: 0.17, 95% CI: 0.02-1.57, P=0.119). Subgroup analysis within the high-risk cohort did not yield a significant association between the positivity rate and recurrence risk (HR=0.43, 95% CI: 0.10-1.79, P=0.246). Discussion In conclusion, this study identifies a nonlinear relationship between the lateral cervical lymph node positivity rate and the risk of DTC recurrence post-treatment. A positivity rate of less than 0.5 is positively associated with recurrence, while this association diminishes in significance among high-risk patients. This differs from the results previously reported. Further studies are needed to determine the potential mechanisms of the associations observed in observational studies.
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Affiliation(s)
- Ting Ye
- Department of Nuclear Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Shihan Shao
- Department of Hepatobiliary Surgery, The Sixth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Shulin Yao
- Department of Nuclear Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
| | - Ruimin Wang
- Department of Nuclear Medicine, The First Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China
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Wang J, Wang J, Liu H, Chen C. Routine Blood Tests as Predictive Tools for Differentiating Follicular Thyroid Carcinoma From Follicular Adenoma. Int J Gen Med 2025; 18:733-744. [PMID: 39963518 PMCID: PMC11830949 DOI: 10.2147/ijgm.s502626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 02/04/2025] [Indexed: 02/20/2025] Open
Abstract
Background Thyroid cancer is the most common endocrine malignancy, with an increasing incidence rate, particularly among adolescents. Follicular thyroid carcinoma (FTC), though less common than papillary thyroid carcinoma (PTC), presents greater diagnostic challenges, especially when differentiating from follicular adenoma (FA). Current diagnostic methods lack specificity, underscoring the need for a simple, cost-effective predictive model for FTC.This study aimed to develop a predictive scoring system based on routine blood biomarkers to distinguish between FTC and FA, facilitating early diagnosis and treatment. Methods A retrospective, single-center case-control study was conducted on patients diagnosed with FTC and FA at Renmin Hospital of Wuhan University from 2016 to 2022. Patients' demographic, clinicopathological characteristics, and preoperative blood biomarker data were analyzed. Statistical tests, including chi-square, t-tests, and Mann-Whitney U-tests, were used to compare biomarkers. Significant variables were included in univariate and multivariate logistic regression analyses, leading to the development of a scoring system. The model's performance was assessed using receiver operating characteristic (ROC) curves. Results The study included 23 patients with FA and 26 patients with FTC. Seven blood biomarkers showed significant differences between the groups: ALB, DBIL, TBIL, LYM#, MCHC, RDW-SD, and WBC. Multivariate logistic regression identified ALB and WBC as key predictors, forming a scoring model (Score = 0.54 × ALB - 1.10 × WBC). The model exhibited strong predictive performance (AUC = 0.839), with sensitivity and specificity of 0.808 and 0.826, respectively. Conclusion The study developed a novel predictive model using routine blood biomarkers, offering a non-invasive, cost-effective tool for differentiating between FTC and FA. The model has significant clinical potential, providing a feasible alternative to conventional diagnostic techniques. Further multicenter studies and mechanistic investigations are warranted to validate and refine the model, enhancing its utility in clinical practice.
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Affiliation(s)
- Jiaxi Wang
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Jingwei Wang
- Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
| | - Hanqing Liu
- Department of Thyroid Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China
| | - Chuang Chen
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China
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Luo Y, Wei W, Huang Y, Li J, Qin W, Hao Q, Ye J, Zhang Z, Liang Y, Xiao X, Cai Y. A new signature associated with anoikis predicts the outcome and immune infiltration in nasopharyngeal carcinoma. Discov Oncol 2025; 16:123. [PMID: 39913001 PMCID: PMC11802990 DOI: 10.1007/s12672-025-01869-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 02/03/2025] [Indexed: 02/07/2025] Open
Abstract
BACKGROUND Previous studies have confirmed the phenomenon of anoikis resistance in nasopharyngeal carcinoma (NPC). Nevertheless, the prognostic significance of anoikis-related genes (ARGs) in NPC remains incompletely understood. This study aimed to create a predictive risk score using an ARGs signature for NPC patients and to investigate how this score relates to clinicopathologic features and immune infiltration in the tumor microenvironment. METHODS By using data from the Gene Expression Omnibus (GEO) database, we employed machine learning methods to discover prognostic ARGs and create a risk score. Key gene expression levels were validated through real-time PCR and immunohistochemical staining. RESULTS Three differentially expressed ARGs (CDC25C, E2F1 and RBL2) with prognostic value were identified by the intersection of multiple machine learning algorithms. A risk score based on t 3-ARG feature was developed to stratify NPC patients into two distinct risk groups using the optimal model, Random Survival Forest. NPC patients with high-risk scores experienced notably shorter progression-free survival in comparison to those with low-risk scores. Multivariate Cox regression analysis indicated that the risk score served as an independent prognostic factor. The time-dependent ROC and decision curve analyses demonstrated the risk model's strong predictive accuracy and clinical utility. The low-risk score group exhibited features indicative of early clinical stage, immune activation, high immune checkpoint gene's expression, and low Epstein-Barr virus gene's expression. Functional analysis revealed enrichment of immune-related pathways in the low-risk group. Patients with high-risk scores were discovered to be unlikely to benefit from immune checkpoint inhibitor treatment. Moreover, the expression of RBL2, E2F1, and CDC25C were significantly correlated with the expression of caspase family genes. Finally, the lower mRNA and protein expression of RBL2 were validated in NPC cell lines and tissues. CONCLUSIONS Our ARGs-based signature model shows promising results in predicting the prognosis of NPC patients and might be associated with immune cell infiltration.
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Affiliation(s)
- Yonglin Luo
- Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
| | - Wenyang Wei
- School of Clinical Medicine, Guilin Medical University, Guilin, China
| | - Yaxuan Huang
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jun Li
- Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
| | - Weiling Qin
- Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
| | - Quanxiang Hao
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
| | - Jiemei Ye
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China
| | - Zhe Zhang
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yushan Liang
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xue Xiao
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, China
- Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yonglin Cai
- Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China.
- Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, Guangxi, China.
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Huang F, Wei R, Mei S, Xiao T, Zhao W, Zheng Z, Liu Q. Clinical calculator based on clinicopathological characteristics predicts local recurrence and overall survival following radical resection of stage II-III colorectal cancer. Front Oncol 2025; 15:1494255. [PMID: 39975593 PMCID: PMC11835698 DOI: 10.3389/fonc.2025.1494255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Accepted: 01/13/2025] [Indexed: 02/21/2025] Open
Abstract
Purpose This study aimed to analyze the risk factors and survival prognosis of local recurrence in stage II-III colorectal cancer (CRC) and develop a clinical risk calculator and nomograms to predict local recurrence and survival in treated patients. Methods Patients who underwent radical surgery between January 2009 and December 2019 at the China National Cancer Center were included. Multivariate nomograms and a clinical risk calculator based on Cox regression were developed. Discrimination was measured with an area under curve (AUC) and variability in individual predictions was assessed with calibration curves. We stratified patients into different risk groups according to the established model to predict their prognosis and guide clinical practice. Results The clinical risk calculator incorporated six variables: tumor thrombus, perineural invasion, tumor grade, pathology T-stage, pathology N-stage, and whether more than 12 lymph nodes were harvested. Our clinical risk calculator provided good discrimination, with AUC values of local recurrence-free survival (LRFS) (0.764) and overall survival (OS) (0.815) in the training cohort and LRFS (0.740) and OS (0.730) in the test cohort. Calibration plots illustrated excellent agreement between the clinical risk calculator predictions and actual observations for 3- and 5-year LRFS and OS. Recurrence risk-stratified analysis showed that low-risk patients were more likely to undergo salvage radical surgery when recurrent disease existed. Conclusion The clinical calculator can better account for tumor and patient heterogeneity, providing a more individualized outcome prognostication. The model is expected to aid in treatment planning, such as resectability evaluation, and it can be used in postoperative surveillance (https://oldcoloncancer.shinyapps.io/dynnomapp/).
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Affiliation(s)
- Fei Huang
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ran Wei
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shiwen Mei
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Tixian Xiao
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Zhao
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhaoxu Zheng
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qian Liu
- Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Wang M, Xu Y, Yang BX, Luo D, Hou H, Liu Q. A longitudinal study of resilience and social function in patients with colorectal cancer and stomas. J Psychosom Res 2025; 189:112013. [PMID: 39671855 DOI: 10.1016/j.jpsychores.2024.112013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 12/08/2024] [Accepted: 12/09/2024] [Indexed: 12/15/2024]
Abstract
OBJECTIVE To explore the dynamic changes, influencing factors, and relationships between resilience and social function in patients with colorectal cancer (CRC) and stomas at different postoperative stages, and to inform precise psychosocial rehabilitation interventions. METHODS A longitudinal study was conducted at a tertiary hospital in eastern China from January 2021 to June 2023. Patients completed a self-designed socio-demographic questionnaire one month post-surgery, and the Connor and Davidson Resilience Scale (CD-RISC) and Social Dysfunction Screening Scale (SDSS) at 1, 3, and 5 months post-surgery. Data were analyzed using repeated measures ANOVA, Spearman correlation, group-based trajectory modeling, and binary logistic regression. RESULTS A total of 131 patients were included in the analysis. Resilience showed an initial increase followed by a decline, while social function consistently improved. A moderate negative correlation between social dysfunction and resilience was observed at all time points. Influencing factors for resilience and social function varied across different postoperative stages. Significant differences in resilience trajectories were observed based on education and family income. Resilience trajectories significantly impacted social function trajectories (OR 19.39, 95 % CI 2.46-152.91, P < 0.05). CONCLUSIONS This study identifies distinct trajectories of resilience and social function in patients with colorectal cancer and stomas. Low resilience is linked to severe social function deficits. Stage-specific interventions are crucial to enhance social adaptation and improve overall quality of life. Tailored support is needed throughout recovery to address the unique challenges faced by these patients.
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Affiliation(s)
- Min Wang
- School of Nursing, Wuhan University, Wuhan, China; Department of General Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China
| | - Yanhua Xu
- Department of General Surgery, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China
| | | | - Dan Luo
- School of Nursing, Wuhan University, Wuhan, China
| | - Hao Hou
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qian Liu
- School of Nursing, Wuhan University, Wuhan, China.
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Xiao C, Xu R, Luo Y, Xu Z, Tang C. Is second 131I treatment necessary for differentiated thyroid cancer patients and who could not benefit from it? A real-world retrospective study in China. Ann Nucl Med 2025; 39:167-175. [PMID: 39313672 DOI: 10.1007/s12149-024-01984-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 09/18/2024] [Indexed: 09/25/2024]
Abstract
BACKGROUND The efficacy of a second radioactive iodine-131 (131I) treatment in patients with differentiated thyroid cancer (DTC) who did not achieve an excellent response (ER) following initial 131I therapy remains controversy and the population that would derive limited benefit from it is currently unclear. OBJECTIVES The aim of this retrospective study was to assess the efficacy of the second 131I treatment in DTC patients with non-ER after the initial 131I therapy, and to identify potential risk factors associated with non-benefit of the second 131I treatment. METHODS 127 DTC patients who underwent two 131I treatments following thyroidectomy were included in this study, and the therapeutic response was evaluated after each 131I treatment. Beneficial treatment was defined as an improvement in therapy response grade (e.g. from indeterminate response to ER) after the second 131I treatment, while unbeneficial treatment was defined as no change or a downgrade in therapy response grade. The potential risk factors associated with the non-benefit of the second 131I treatment were identified using univariate and multivariate logistic regression models. RESULTS Following the second 131I treatment, therapy responses of 55.12% (70/127) of patients were reclassified to a better grade indicating treatment benefit, while 44.88% (57/127) showed no change or were reclassified to a worse grade suggesting no benefit from treatment. The non-benefit of the second 131I treatment was significantly associated with potential risk factors including stimulated thyroglobulin (sTg) level ≥ 11.46 ng/mL before the second 131I treatment, primary tumor size > 2 cm, status T2 or higher, N1b status and ATA high risk. CONCLUSIONS The study results demonstrated that more than half of DTC patients could potentially benefit from a second 131I therapy. However, over 40% of patients exhibited no benefit in response to the second 131I treatment, suggesting potential overtreatment for this subgroup. Therefore, clinicians should exercise meticulous and precise decision-making based on identified risk factors when considering the necessity of a second 131I treatment.
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Affiliation(s)
- Canran Xiao
- Department of Nuclear Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China
- Department of Nuclear Medicine, Chongqing University Cancer Hospital, Chongqing, 400030, China
| | - Ruoxin Xu
- Department of Nuclear Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China
| | - Yao Luo
- Department of Nuclear Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China
| | - Zeqing Xu
- Department of Nuclear Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China
| | - Caihua Tang
- Department of Nuclear Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, China.
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Wu A, Guo Z, Lin Y, Chi J, Lan Y, Lou Q, Zhang H, Chen Y. Trends in incidence, mortality and survival of gastric cancer in Xiamen, China from 2011 to 2020: A population-based study. Cancer Epidemiol 2025; 94:102718. [PMID: 39615306 DOI: 10.1016/j.canep.2024.102718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 11/14/2024] [Accepted: 11/22/2024] [Indexed: 01/22/2025]
Abstract
BACKGROUND Gastric cancer remains one of the most common cancers and the leading cause of death in China. This study aims to describe the incidence, mortality, survival rates, and their changing trends of gastric cancer in Xiamen, China from 2011 to 2020. METHODS Population-based cancer registry data were used to calculate the incidence, mortality, and survival rates of gastric cancer. The study population consisted of gastric cancer patients diagnosed from January 1, 2011, to December 31, 2020, and followed up until September 30, 2023. The relative survival of gastric cancer was calculated using period methods. The change in trends was analyzed using Joinpoint regression. RESULTS From 2011-2020, a total of 4716 new cases of gastric cancer and 3520 related deaths were reported. The crude incidence rate and age-standardized incidence rate (ASIR) were 21.82/100,000 and 16.74/100,000. The crude mortality rate and age-standardized mortality rate (ASMR) were 16.29/100,000 and 12.30/100,000. The ASIR and ASMR in males (ASIR: 24.71/100,000, ASMR: 18.75/100,000) were both more than those in females (ASIR: 9.6/100,000, ASMR: 6.55/100,000). The observed 5-year survival rate was 25.83 %, with an age standardized survival of 27.60 %. The incidence and mortality of gastric cancer showed a decreasing trend, and the 5-year ARS between 2016 and 2020 (30.03 %, 95 %CI: 28.07-32.12 %) was higher than between 2011 and 2015 ( 24.79 %, 95 %CI: 22.53-27.27 %). Furthermore, the survival rate decreased with increasing age. CONCLUSIONS From 2011-2020, the incidence and mortality of gastric cancer in Xiamen City have shown a decreasing trend, and the survival rate has significantly improved. Despite improved survival, the 5-year ARS remains low.
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Affiliation(s)
- Ahua Wu
- Xiamen City Center for Disease Control and Prevention, Xiamen, Fujian, China
| | - Zhinan Guo
- Xiamen City Center for Disease Control and Prevention, Xiamen, Fujian, China
| | - Yilan Lin
- Xiamen City Center for Disease Control and Prevention, Xiamen, Fujian, China
| | - Jiahuang Chi
- Xiamen City Center for Disease Control and Prevention, Xiamen, Fujian, China
| | - Yanqi Lan
- Xiamen City Center for Disease Control and Prevention, Xiamen, Fujian, China
| | - Qun Lou
- Xiamen City Center for Disease Control and Prevention, Xiamen, Fujian, China
| | - Haixia Zhang
- Xiamen City Center for Disease Control and Prevention, Xiamen, Fujian, China.
| | - Youlan Chen
- Xiamen City Center for Disease Control and Prevention, Xiamen, Fujian, China.
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Guo Y, Huang Q, Heng Y, Zhou Y, Chen H, Xu C, Wu C, Tao L, Zhou L. Circular RNAs in cancer. MedComm (Beijing) 2025; 6:e70079. [PMID: 39901896 PMCID: PMC11788016 DOI: 10.1002/mco2.70079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 12/23/2024] [Accepted: 01/09/2025] [Indexed: 02/05/2025] Open
Abstract
Circular RNA (circRNA), a subtype of noncoding RNA, has emerged as a significant focus in RNA research due to its distinctive covalently closed loop structure. CircRNAs play pivotal roles in diverse physiological and pathological processes, functioning through mechanisms such as miRNAs or proteins sponging, regulation of splicing and gene expression, and serving as translation templates, particularly in the context of various cancers. The hallmarks of cancer comprise functional capabilities acquired during carcinogenesis and tumor progression, providing a conceptual framework that elucidates the nature of the malignant transformation. Although numerous studies have elucidated the role of circRNAs in the hallmarks of cancers, their functions in the development of chemoradiotherapy resistance remain unexplored and the clinical applications of circRNA-based translational therapeutics are still in their infancy. This review provides a comprehensive overview of circRNAs, covering their biogenesis, unique characteristics, functions, and turnover mechanisms. We also summarize the involvement of circRNAs in cancer hallmarks and their clinical relevance as biomarkers and therapeutic targets, especially in thyroid cancer (TC). Considering the potential of circRNAs as biomarkers and the fascination of circRNA-based therapeutics, the "Ying-Yang" dynamic regulations of circRNAs in TC warrant vastly dedicated investigations.
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Affiliation(s)
- Yang Guo
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Qiang Huang
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Yu Heng
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Yujuan Zhou
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Hui Chen
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Chengzhi Xu
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Chunping Wu
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Lei Tao
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
| | - Liang Zhou
- ENT Institute and Department of Otorhinolaryngology Eye & ENT Hospital, Fudan University Xuhui District Shanghai China
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Zuo X, Li H, Xie S, Shi M, Guan Y, Liu H, Yan R, Zheng A, Li X, Liu J, Gan Y, Shi H, Chen K, Jia S, Chen G, Liao M, Wang Z, Han Y, Liao B. A prognostic model of 8-T/B cell receptor-related signatures for hepatocellular carcinoma. Discov Oncol 2025; 16:105. [PMID: 39890709 PMCID: PMC11785873 DOI: 10.1007/s12672-025-01856-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 01/28/2025] [Indexed: 02/03/2025] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The T cell receptor (TCR) and B cell receptor (BCR) are the receptors on the surface of T or B cell, which are crucial for recognizing tumor antigens. It is profound to establish a practical TCR/BCR-related gene signature prognostic model for the further diagnosis and treatment among HCC patients. METHODS In this study, we categorized gene expression data of HCC patients from The Cancer Genome Altas and identified TCR related genes by the Least Absolute Shrinkage and Selection Operator and multivariate Cox regression analysis. Both the CIBERSORT algorithm and the TB tools were used to analyze the features and heterogeneity of the tumor microenvironment. RESULTS Finally, an 8-gene prognostic model was successfully established and achieved the validation in both the International Cancer Genome Consortium and Nanfang Hospital cohorts. Patients were divided into high-risk and low-risk groups based on the median of the risk scores. We observed that tumor differentiation was worse while the fibrinogen concentration was higher in the high-risk group of patients. Both the number of unique TCR and BCR clonotypes and the expanded clones were higher in the low-risk group than in the high-risk group. CONCLUSIONS Together, our study screened a TCR/BCR-related signature prognostic model, which might turn into a beneficial and practical tool to solve the perplexities of the treatment, prognosis prediction and management for HCC patients.
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Affiliation(s)
- Xuan Zuo
- Department of Hepatology, Guangzhou Institute of Clinical Medicine of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, China
| | - Hui Li
- HRYZ Biotech Co., Shenzhen, China
| | - Shi Xie
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Mengfen Shi
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yujuan Guan
- Department of Hepatology, Guangzhou Institute of Clinical Medicine of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, China
| | - Huiyuan Liu
- Department of Hepatology, Guangzhou Institute of Clinical Medicine of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, China
| | - Rong Yan
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Anqi Zheng
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xueying Li
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jiabang Liu
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yifan Gan
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Haiyan Shi
- Department of Hepatology, Guangzhou Institute of Clinical Medicine of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, China
| | - Keng Chen
- Department of Hepatology, Guangzhou Institute of Clinical Medicine of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, China
| | - Shijie Jia
- Department of Hepatology, Guangzhou Institute of Clinical Medicine of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, China
| | - Guanmei Chen
- Department of Hepatology, Guangzhou Institute of Clinical Medicine of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, China
| | - Min Liao
- Department of Hepatology, Guangzhou Institute of Clinical Medicine of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, China
| | - Zhanhui Wang
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | | | - Baolin Liao
- Department of Hepatology, Guangzhou Institute of Clinical Medicine of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510440, China.
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Chen P, Hou W, Li C, Liang Q, Ma L, Zhao X, Yi C. Lived experiences of patients with advanced pancreatic cancer on patient-reported outcomes (PROs) management: a qualitative phenomenological study in Southwest China. BMJ Open 2025; 15:e084259. [PMID: 39880447 PMCID: PMC11781101 DOI: 10.1136/bmjopen-2024-084259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Accepted: 01/08/2025] [Indexed: 01/31/2025] Open
Abstract
OBJECTIVES To explore the lived experiences of patients with advanced pancreatic cancer enrolled in a patient-reported outcomes (PROs) management programme and to preliminarily understand how PROs management influences various aspects of patient care and overall quality of life. DESIGN A qualitative phenomenological study. SETTING A national cancer care centre in Southwest China specialised in cancer care, with a comprehensive PROs management programme. PARTICIPANTS 15 participants diagnosed with advanced pancreatic cancer. RESULTS Five key themes emerged from our interviews, including enhanced communication with healthcare providers, attributed to the structured nature of PROs; increased perceived sense of care, with patients feeling more valued and heard; PROs management facilitated better treatment decision-making, with patients feeling more involved and empowered; improved communication with family members, aiding in better understanding and support; and varied perceptions of the impact on quality of life, with some noting improvements in specific aspects like symptom management, while others were uncertain about the overall benefit. CONCLUSIONS PROs management plays a significant role in improving communication between patients with advanced pancreatic cancer and their healthcare providers, enhancing patients' involvement in treatment decisions, and potentially improving family dynamics. However, the impact of PROs management on the overall quality of life of patients remains complex and individualised. The findings suggest that further research with a more diverse patient population is needed to fully understand the implications of PROs management in advanced cancer care.
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Affiliation(s)
- Ping Chen
- Department of Oncology, Chengdu Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan, China
| | - Wanting Hou
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Changlin Li
- Department of Oncology, Chengdu Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan, China
| | - Qingyue Liang
- Clinical Nutrition Department, Chengdu Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan, China
| | - Li Ma
- Department of Oncology, Chengdu Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan, China
| | - Xiumei Zhao
- Department of Oncology, Chengdu Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, Sichuan, China
| | - Cheng Yi
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Zheng S, Lin Z, Zhang R, Cheng Z, Li K, Gu C, Chen Y, Lin J. Progress in immunotherapy for brain metastatic melanoma. Front Oncol 2025; 14:1485532. [PMID: 39935851 PMCID: PMC11810730 DOI: 10.3389/fonc.2024.1485532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 11/07/2024] [Indexed: 02/13/2025] Open
Abstract
Melanoma is highly aggressive, with brain metastasis being a significant contributor to poor outcomes. Immunotherapy has emerged as a crucial treatment modality for melanoma, particularly for addressing brain metastases. This review explores recent developments in immunotherapy for patients with melanoma brain metastasis, with such treatments encompassing immune checkpoint inhibitors and various immunotherapy combination approaches, such as dual immunotherapy, immunotherapy combined with chemotherapy, immunotherapy combined with targeted drugs, and immunotherapy combined with radiotherapy. This article also discusses existing treatment obstacles and potential future avenues for research and clinical practice.
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Affiliation(s)
- Shicheng Zheng
- School of Basic Medicine, Fujian Medical University, Fuzhou, Fujian, China
| | - Zhongqiao Lin
- Phase I Clinical Trial Ward, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Ruibo Zhang
- School of Basic Medicine, Fujian Medical University, Fuzhou, Fujian, China
| | - Zihang Cheng
- School of Basic Medicine, Fujian Medical University, Fuzhou, Fujian, China
| | - Kaixin Li
- School of Basic Medicine, Fujian Medical University, Fuzhou, Fujian, China
| | - Chenkai Gu
- School of Basic Medicine, Fujian Medical University, Fuzhou, Fujian, China
| | - Yu Chen
- Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
- Cancer Bio-Immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Jing Lin
- Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
- Cancer Bio-Immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
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Fu Y, Sang J, Zhang F, Jiang S, Li F, Liang T, Xu C. Exosomal tRF-1003 induces angiogenesis via regulating the HIF1α/VEGF signaling in multiple myeloma. Int Immunopharmacol 2025; 146:113862. [PMID: 39689600 DOI: 10.1016/j.intimp.2024.113862] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/07/2024] [Accepted: 12/11/2024] [Indexed: 12/19/2024]
Abstract
BACKGROUND Multiple myeloma (MM) remains a therapeutically challenging hematologic malignancy characterized by frequent relapse and disease progression. Angiogenesis regulated by non-coding RNAs plays a vital role in MM pathogenesis. Despite the potential clinical applications of tsRNAs, the specific mechanisms by which they contribute to MM progression, particularly through angiogenesis within the bone marrow microenvironment, remain elusive. METHODS In this study, we focused on the role of exosomal tRF-1003 in MM progression. Serum and bone marrow samples from relapsed and refractory multiple myeloma (R/RMM) and newly diagnosed multiple myeloma (NDMM) patients were analyzed for tsRNA expression. Functional assays, including transwell migration, wound-healing assays, and in vivo tumor formation studies, were employed to assess the angiogenic potential of tRF-1003 in HUVEC. Mechanistic studies were conducted to understand how tRF-1003 modulates the HIF-1α/VEGF signaling pathway through interaction with MAPK1. RESULTS We found that tRF-1003 was significantly upregulated in serum exosomes derived from R/RMM patients. Exosomal tRF-1003 was efficiently delivered to endothelial cells, leading to enhanced angiogenesis both in vitro and in vivo. Mechanistically, tRF-1003 was shown to activate HIF-1α/VEGF signaling in endothelial cells by downregulating MAPK1 expression, thereby promoting angiogenesis. Overexpression of MAPK1 in endothelial cells partially reversed the angiogenic effects induced by exosomal tRF-1003. CONCLUSION Our findings reveal that exosomal tRF-1003 plays a pivotal role in MM angiogenesis by modulating the HIF-1α/VEGF signaling pathway through MAPK1. These insights provide a novel perspective on the mechanisms driving MM progression and highlight the potential therapeutic value of targeting tRF-1003 in managing multiple myeloma.
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Affiliation(s)
- Yunfeng Fu
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha 410000, China; Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha 410000, China
| | - Jianyao Sang
- Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha 410000, China
| | - Fangrong Zhang
- Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha 410000, China
| | - Siyi Jiang
- Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha 410000, China
| | - Fangfang Li
- Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha 410000, China
| | - Ting Liang
- Department of Blood Transfusion, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518000, China.
| | - Cong Xu
- Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518000, China.
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Han S, Jiang H, Wang J, Li C, Liu T, Xuan M, Tian B, Si Y, Zhao H, Zhao Y, Zhu Z, Yu W, Wang L. WTAP-Mediated N6-Methyladenosine Modification Promotes Gastric Cancer Progression by Regulating MAP2K6 Expression. J Cancer 2025; 16:1420-1437. [PMID: 39991580 PMCID: PMC11843227 DOI: 10.7150/jca.98559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 01/12/2025] [Indexed: 02/25/2025] Open
Abstract
Wilms tumor 1 associated protein (WTAP) is a key RNA N6-methyladenosine (m6A) methylase, which is involved in gastric cancer (GC) development, but its pathogenic mechanism is not clear. This study aims to thoroughly explore the underlying molecular mechanism of WTAP-mediated m6A modification in GC pathogenesis. qRT-PCR and immunohistochemistry showed that significantly elevated WTAP expression in GC tissues and is related to advanced age, poorly differentiation, lymph node metastasis and high TNM stage. Overexpression and knockdown of WTAP could promote or inhibit the proliferation, migration and invasion of GC cells in vitro, furthermore, suppression of WTAP expression impeded the growth of xenograft tumors in vivo. Utilizing RNA sequencing, methylated RNA immunoprecipitation (MeRIP) sequencing and bioinformatics analysis, we identified MAP2K6 as direct downstream target of WTAP with m6A modification in GC. The interaction between WTAP and MAP2K6 was confirmed by MeRIP-qPCR, luciferase reporter assay, Co-IF and bioinformatics prediction. Immunofluorescence and rescue studies were performed to verify WTAP-mediated m6A modification promotes the proliferation, migration, and invasion of GC cells by positively regulating the target gene MAP2K6. This underscores the potential therapeutic significance of targeting the WTAP-MAP2K6 axis in combating GC occurrence and progression.
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Affiliation(s)
- Shuangshuang Han
- Department of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Haibin Jiang
- Department of Gastroenterology, Chengde Central Hospital, Chengde, China
| | - Jia Wang
- Department of Internal Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Chao Li
- Department of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Ting Liu
- Department of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Mingda Xuan
- Department of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Bo Tian
- Department of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yi Si
- Department of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hongyan Zhao
- Department of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yunxia Zhao
- Department of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhenlong Zhu
- Department of Pathology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Weifang Yu
- Department of Endoscopy Center, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Lihong Wang
- Department of Internal Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, China
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Liu J, Gao W, Zheng X, Wu S, Shi Y, Wang F, Wu Y. Molecular testing stratifies the risk of structural recurrence in high risk differentiated thyroid cancer: a retrospective cohort study. Front Endocrinol (Lausanne) 2025; 16:1508404. [PMID: 39926346 PMCID: PMC11802368 DOI: 10.3389/fendo.2025.1508404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 01/02/2025] [Indexed: 02/11/2025] Open
Abstract
Background High-risk differentiated thyroid cancer in 2015 American Thyroid Association risk stratification system (ATA-RSS) exhibits a significantly increased probability of recurrence and poor outcomes. This study aimed to investigate the molecular profiles of high-risk differentiated thyroid cancer and to assess the role of molecular testing in enhancing prognostic risk stratification. Methods In a single-center study conducted at Fujian Cancer Hospital, Fujian Province, China, a consecutive cohort of differentiated thyroid cancer patients identified as high-risk under 2015 ATA-RSS criteria were retrospectively assessed, spanning from November 1, 2019, to March 31, 2022. Molecular characterize groups were conducted using an 18-gene next-generation sequencing assay. Patients harboring mutations in the TERT promoter, TP53, or PIK3CA genes were categorized as the high molecular risk group, while all others were assigned to the non-high molecular risk group. Results Among the 108 cases, 32 (29.6%) fell into the high molecular risk group, characterized by a significantly older mean age (57.8 vs. 42.6 years, p < 0.001), larger tumor size (3.1 cm vs. 2.0 cm, p = 0.003), a higher incidence of aggressive pathological subtypes (43.8% vs. 7.9%, p < 0.001), and an increased occurrence of distant metastasis (34.4% vs. 7.9%, p = 0.001). Over a median follow-up period of 32.5 months, this high-risk group demonstrated an elevated risk of local recurrence (32.1% vs. 9.5%, HR: 3.18, 95% CI: 1.15-8.78) and metachronous distant metastasis (38.1% vs. 2.9%, HR: 12.54, 95% CI: 2.60-60.41). Multivariate COX regression analysis confirmed that molecular characterize groups (HR: 5.77, 95% CI: 2.18-15.23, p < 0.001) and tumor size (HR: 1.32, 95% CI: 1.00-1.74, p = 0.047) independently predicted recurrence-free survival. Conclusion ATA-RSS high-risk differentiated thyroid cancer often presents with late-hit genetic alterations, which are strongly associated with increased likelihood of structural recurrence. Molecular testing offers a precise approach to recurrence risk stratification in high-risk cases, enabling personalized follow-up and treatment strategies tailored to the specific prognostic profile.
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Affiliation(s)
- Jie Liu
- Department of Head and Neck Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Wensi Gao
- Department of Breast Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Xiong Zheng
- Department of Head and Neck Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Shuping Wu
- Department of Head and Neck Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Yi Shi
- Department of Molecular Pathology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Feng Wang
- Department of Head and Neck Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
| | - Yu Wu
- Department of Head and Neck Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
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Yang Z, Wang Q, Yi F, Zhang L, Li Y, Rong L, Wan S. What are the problems and suggestions related to cancer health education in Sichuan, China? A qualitative study of community health workers (CHWs). BMC Health Serv Res 2025; 25:136. [PMID: 39856689 PMCID: PMC11761214 DOI: 10.1186/s12913-024-11835-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 10/24/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Health education conducted by community health workers (CHWs) is an evidence-based strategy for promoting cancer prevention, cancer screening, and adherence to medical guidance from doctors. However, CHWs are confronted with some problems related to cancer health education in China. This study aimed to clarify CHWs' awareness of problems in cancer health education in China and the solutions that they were considering to improve the quality and efficiency of cancer health education. METHODS A qualitative descriptive design with purposive sampling was applied in eight primary health care sectors in Guangyuan and Chengdu in Sichuan, China. Face-to-face, in-depth, semistructured interviews were conducted, and a total of 60 CHWs were interviewed. The interviews were transcribed verbatim and imported into Nvivo12.0. Thematic analysis using the constant comparative method was used to analyze the data. RESULTS Uncooperative inhabitants, poor organization, low-frequency provision, and inadequate training for CHWs were problems related to cancer health education provided by CHWs in China. CHWs proposed some suggestions to improve the accessibility and acceptability of cancer health education, including combining online and offline education, health education after screening, cancer plus others, health education in the workplace, and volunteer recruitment. CONCLUSIONS Both the problems and suggestions described in this study may provide evidence for cancer health education and policy-making related to cancer prevention and control in China.
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Affiliation(s)
- Zhonghua Yang
- Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, P. R. China
| | - Qingqing Wang
- Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, P. R. China
| | - Fang Yi
- Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, P. R. China
| | - Linglin Zhang
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, P. R. China
| | - Yuting Li
- School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, P. R. China
| | - Lilou Rong
- Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, P. R. China
| | - Shaoping Wan
- Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, 610041, P. R. China.
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Fang G, Pi Z, An Y, Cao X, Li W, Zhu X, Ding J. Cost-effectiveness analysis of gumarontinib versus savolitinib for the treatment of advanced or metastatic NSCLC with MET exon 14 skipping mutations in China using partitioned survival model. Front Pharmacol 2025; 16:1400422. [PMID: 39925845 PMCID: PMC11802428 DOI: 10.3389/fphar.2025.1400422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 01/03/2025] [Indexed: 02/11/2025] Open
Abstract
Background and objectives Both gumarontinib and savolitinib have demonstrated efficacy in treating non-small-cell lung cancer (NSCLC) with tumors harboring mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping. However, the comparison of their efficacy and pharmacoeconomics profiles remains limited. This study aims to evaluate the cost-effectiveness of gumarontinib versus savolitinib for the treatment of METex14 skipping NSCLC in China. Methods A 3-state partitioned survival model (PSM) was developed with lifetime horizon from the perspective of Chinese healthcare system. Survival inputs were based on an unanchored matching-adjusted indirect comparison using individual patient data from GLORY trial to adjust for patient characteristics in NCT02897479. Costs and outcomes were discounted at an annual rate of 5%. Sensitivity and scenario analyses were conducted to explore model uncertainty. Results Gumarontinib gained an additional 0.10 QALYs at an incremental cost of $1,893 compared to savolitinib, resulting in the ICERs of $19,243/QALY, which is below the threshold of 3 times the GDP per capita in China ($35,007 per capita in 2022). Sensitivity and scenario analyses confirmed the robustness of the base-case results. Conclusion Gumarontinib is a cost-effective option compared to savolitinib for METex14 skipping NSCLC in China.
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Affiliation(s)
- Gang Fang
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China
| | - Zhipeng Pi
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China
| | - Yiping An
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China
| | - Xinxin Cao
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China
| | - Wei Li
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China
- Pharmaceutical Market Access Policy Research Center, China Pharmaceutical University, Nanjing, China
| | - Xiangjun Zhu
- Jiangsu Health Development Research Center, Nanjing, China
| | - Jinxi Ding
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China
- Pharmaceutical Market Access Policy Research Center, China Pharmaceutical University, Nanjing, China
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Tian W, Su X, Hu C, Chen D, Li P. Ferroptosis in thyroid cancer: mechanisms, current status, and treatment. Front Oncol 2025; 15:1495617. [PMID: 39917169 PMCID: PMC11798778 DOI: 10.3389/fonc.2025.1495617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 01/06/2025] [Indexed: 02/09/2025] Open
Abstract
Thyroid cancer (TC) represents the most prevalent malignancy within the endocrine system. In recent years, there has been a marked global increase in the incidence of thyroid cancer, garnering substantial scientific interest. Comprehensive investigations into the pathogenesis of TC have identified a significant association with ferroptosis, a newly characterized form of cell death mediated by iron ions. Distinct from apoptosis, necrosis, and autophagy, ferroptosis is characterized by the accumulation of lipid peroxides and reactive oxygen species, culminating in cellular damage and death.Recent research has elucidated a connection between ferroptosis and the initiation, progression, and treatment of thyroid cancer. These findings underscore the significance of ferroptosis in thyroid cancer and offer valuable insights into the development of novel therapeutic strategies and precise predictive markers. The unique mechanisms of ferroptosis present opportunities for targeting treatment-resistant thyroid cancers. Consequently, the regulation of ferroptosis may emerge as a novel therapeutic target, potentially addressing the limitations of current treatments. Moreover, elucidating the molecular mechanisms underpinning ferroptosis in thyroid cancer may facilitate the identification of novel biomarkers for early detection and prognostication. This review endeavors to synthesize the extant knowledge regarding the role of ferroptosis in thyroid cancer, examine potential therapeutic implications, and propose future research trajectories to enhance the understanding and clinical application of ferroptosis.
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Affiliation(s)
- Wenzhi Tian
- Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Peking University-The Hong Kong University of Science and Technology Medical Centre, Shenzhen, Guangdong, China
- Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, China
| | - Xi Su
- Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Peking University-The Hong Kong University of Science and Technology Medical Centre, Shenzhen, Guangdong, China
| | - Chenchen Hu
- Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Peking University-The Hong Kong University of Science and Technology Medical Centre, Shenzhen, Guangdong, China
| | - Dong Chen
- Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Peking University-The Hong Kong University of Science and Technology Medical Centre, Shenzhen, Guangdong, China
| | - Peng Li
- Department of Thyroid and Breast Surgery, Peking University Shenzhen Hospital, Peking University-The Hong Kong University of Science and Technology Medical Centre, Shenzhen, Guangdong, China
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Xiao B, Yang M, Meng Y, Wang W, Chen Y, Yu C, Bai L, Xiao L, Chen Y. Construction of a prognostic prediction model for colorectal cancer based on 5-year clinical follow-up data. Sci Rep 2025; 15:2701. [PMID: 39838027 PMCID: PMC11750956 DOI: 10.1038/s41598-025-86872-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 01/14/2025] [Indexed: 01/23/2025] Open
Abstract
Colorectal cancer (CRC) is a prevalent malignant tumor that presents significant challenges to both public health and healthcare systems. The aim of this study was to develop a machine learning model based on five years of clinical follow-up data from CRC patients to accurately identify individuals at risk of poor prognosis. This study included 411 CRC patients who underwent surgery at Yixing Hospital and completed the follow-up process. A modeling dataset containing 73 characteristic variables was established by collecting demographic information, clinical blood test indicators, histopathological results, and additional treatment-related information. Decision tree, random forest, support vector machine, and extreme gradient boosting (XGBoost) models were selected for modeling based on the features identified through recursive feature elimination (RFE). The Cox proportional hazards model was used as the baseline for model comparison. During the model training process, hyperparameters were optimized using a grid search method. The model performance was comprehensively assessed using multiple metrics, including accuracy, F1 score, Brier score, sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic curve, calibration curve, and decision curve analysis curve. For the selected optimal model, the decision-making process was interpreted using the SHapley Additive exPlanations (SHAP) method. The results show that the optimal RFE-XGBoost model achieved an accuracy of 0.83 (95% CI 0.76-0.90), an F1 score of 0.81 (95% CI 0.72-0.88), and an area under the receiver operating characteristic curve of 0.89 (95% CI 0.82-0.94). Furthermore, the model exhibited superior calibration and clinical utility. SHAP analysis revealed that increased perioperative transfusion quantity, higher tumor AJCC stage, elevated carcinoembryonic antigen level, elevated carbohydrate antigen 19-9 (CA19-9) level, advanced age, and elevated carbohydrate antigen 125 (CA125) level were correlated with increased individual mortality risk. The RFE-XGBoost model demonstrated excellent performance in predicting CRC patient prognosis, and the application of the SHAP method bolstered the model's credibility and utility.
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Affiliation(s)
- Boao Xiao
- School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
- Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Min Yang
- School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
- Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Yao Meng
- School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
- Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Weimin Wang
- Department of Oncology, Yixing Hospital Affiliated to Medical College of Yangzhou University, Yixing, 214200, Jiangsu, China
| | - Yuan Chen
- School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
- Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Chenglong Yu
- School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
- Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Longlong Bai
- School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
- Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Lishun Xiao
- School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
- Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
| | - Yansu Chen
- School of Public Health, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
- Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
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Feng J, Wu C, Shen F, Cai W, Xu B. Second Primary Differentiated Thyroid Carcinoma in Adult Cancer Survivors: A SEER Database Analysis. J Clin Endocrinol Metab 2025; 110:417-428. [PMID: 39047061 DOI: 10.1210/clinem/dgae501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 06/21/2024] [Accepted: 07/18/2024] [Indexed: 07/27/2024]
Abstract
CONTEXT Adult cancer survivors are at a heightened risk for secondary primary differentiated thyroid carcinoma (2-DTC). The characteristics and outcomes of 2-DTC remain poorly understood. OBJECTIVE We aimed to explore the characteristics and outcomes of 2-DTC. METHODS We retrospectively analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2017). 2-DTC was divided into 25 subgroups based on prior primary malignancies (PPMs). Baseline characteristics were compared using the chi-square test. Multivariable logistic analysis was used to identified if PPMs were associated with aggressive DTC characteristics. DTC-specific and cancer-specific mortality were analyzed using a univariable and multivariable competing risk regression model. RESULTS There were 138 555 1-DTC and 9253 2-DTC patients identified. 2-DTC patients were predominantly older, male, and White compared to first primary DTC (1-DTC) (all P < .05). In multivariable logistic regression analysis, only 4 types of PPMs were associated with higher rates of DTC aggressive characteristics, while 19 types exhibited lower rates (all P < .05). In multivariable competing risk analysis, 2-DTC showed no mortality risk in stages I (SHR: 1.16; 95% CI, 0.65-2.07) and II (SHR: 0.67; 95% CI, 0.45-1.01), but a protective role in stages III (SHR: 0.47; 95% CI, 0.27-0.83) and IV (SHR: 0.72; 95% CI, 0.52-0.99). Most PPMs that developed into 2-DTC had a lower risk of DTC-specific death than 1-DTC, but many PPMs had a higher risk of cancer-specific death. CONCLUSION Given the characteristics and outcomes of 2-DTC, aggressive treatment for 2-DTC, particularly for PPM with a high mortality risk, may not be advisable.
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Affiliation(s)
- Jianhua Feng
- Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
- Department of Thyroid Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, P.R. China
| | - Caixiu Wu
- Department of Thyroid Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, P.R. China
| | - Fei Shen
- Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
| | - Wensong Cai
- Department of Thyroid Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, P.R. China
| | - Bo Xu
- Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China
- Department of Thyroid Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, P.R. China
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卢 梓, 黄 方, 蔡 光, 刘 继, 甄 鑫. A multi-constraint representation learning model for identification of ovarian cancer with missing laboratory indicators. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2025; 45:170-178. [PMID: 39819725 PMCID: PMC11744287 DOI: 10.12122/j.issn.1673-4254.2025.01.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Indexed: 01/19/2025]
Abstract
OBJECTIVES To evaluate the performance of a multi-constraint representation learning classification model for identifying ovarian cancer with missing laboratory indicators. METHODS Tabular data with missing laboratory indicators were collected from 393 patients with ovarian cancer and 1951 control patients. The missing ovarian cancer laboratory indicator features were projected to the latent space to obtain a classification model using the representational learning classification model based on discriminative learning and mutual information coupled with feature projection significance score consistency and missing location estimation. The proposed constraint term was ablated experimentally to assess the feasibility and validity of the constraint term by accuracy, area under the ROC curve (AUC), sensitivity, and specificity. Cross-validation methods and accuracy, AUC, sensitivity and specificity were also used to evaluate the discriminative performance of this classification model in comparison with other interpolation methods for processing of the missing data. RESULTS The results of the ablation experiments showed good compatibility among the constraints, and each constraint had good robustness. The cross-validation experiment showed that for identification of ovarian cancer with missing laboratory indicators, the AUC, accuracy, sensitivity and specificity of the proposed multi-constraints representation-based learning classification model was 0.915, 0.888, 0.774, and 0.910, respectively, and its AUC and sensitivity were superior to those of other interpolation methods. CONCLUSIONS The proposed model has excellent discriminatory ability with better performance than other missing data interpolation methods for identification of ovarian cancer with missing laboratory indicators.
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Xu B, Zhang Q, Luo Y, Tong Z, Sun T, Shan C, Liu X, Yao Y, Zhao B, Wang S, Zeng X, Hu C, Yan X, Wang X, Jia H, Chen Z, Qiu F, Wu X, Zhang D, Li T. Lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial. Nat Commun 2025; 16:716. [PMID: 39820749 PMCID: PMC11739584 DOI: 10.1038/s41467-025-56096-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 01/09/2025] [Indexed: 01/19/2025] Open
Abstract
Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2- locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant. Progression-free survival (PFS) assessed by investigators was significantly improved in lerociclib arm versus placebo arm (11.07 vs 5.49 months; hazard ratio, 0.451, 95% CI: 0.311-0.656, P = 0.000016), meeting the pre-specified primary endpoint. The secondary endpoints included PFS assessed by Blinded Independent Central Review (BICR), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), safety and tolerability and pharmacokinetic profile. DOR is not reported, and OS data was immature at the data cut-off but unplanned ad hoc analysis is reported. These findings support lerociclib plus fulvestrant as a treatment option for patients with HR+/HER2- endocrine-resistant advanced breast cancer (ABC). (Funded by Genor Biopharma; LEONARDA-1 ClinicalTrials.gov identifier, NCT05054751.).
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Affiliation(s)
- Binghe Xu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Qingyuan Zhang
- Harbin Medical University Cancer Hospital, Harbin, China
| | - Yang Luo
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhongsheng Tong
- Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Tao Sun
- Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Changping Shan
- The Affiliated Hospital of Jining Medical University, Jining, China
| | - Xinlan Liu
- General Hospital of Ningxia Medical University, Yinchuan, China
| | - Yumin Yao
- Liaocheng People's Hospital, Liaocheng, China
| | - Bing Zhao
- Cancer Hospital of Xinjiang Medical University, Urumuqi, China
| | - Shusen Wang
- Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaohua Zeng
- Breast Cancer Center, Affiliated Cancer Hospital of Chongqing University, Chongqing, China
| | - Changlu Hu
- Anhui Provincial Cancer Hospital, Hefei, China
| | - Xi Yan
- West China Hospital, Sichuan University, Chengdu, China
| | - Xiaojia Wang
- Cancer Hospital of the University of Chinese Academy of Sciences/Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Hangzhou, China
| | - Hongyan Jia
- The First Hospital of Shanxi Medical University, Taiyuan, China
| | - Zhendong Chen
- The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Fuming Qiu
- The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China
| | | | | | - Tong Li
- Genor Biopharma Co., Ltd, Beijing, China
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Yang W, Zhou C, He C, Yang Y, Aiyiti W, Xu L, Shuai C. Defect engineering synergistically boosts the catalytic activity of Fe-MoO v for highly efficient breast mesh antitumor therapy. J Colloid Interface Sci 2025; 678:260-271. [PMID: 39197369 DOI: 10.1016/j.jcis.2024.08.195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 08/10/2024] [Accepted: 08/23/2024] [Indexed: 09/01/2024]
Abstract
The demand for breast mesh with antitumor properties is critical in post-mastectomy breast reconstruction to prevent local tumor recurrence. Molybdenum-based oxide (MoOx) exhibits enzyme-like activities by catalyzing endogenous hydrogen peroxide to produce reactive oxygen species for inducing tumor cell apoptosis. However, its catalytic activity is limited by insufficient active sites. Herein, a defect engineering strategy is proposed to create redox nanozymes with multiple enzymatic activities by incorporating Fe into MoOx (Fe-MoOv). Fe-MoOv is subsequently integrated into polycaprolactone (PCL) to fabricate breast meshes for establishing an enzyme-catalyzed antitumor platform. The doping of Fe into MoOx formed numerous defect sites, including oxygen vacancies (OV) and Fe substitution sites, synergistically boosting the binding capacity and catalytic activity of Fe-MoOv. Density functional theory calculations demonstrated that the outstanding peroxidase-like catalytic activity of Fe-MoOv resulted from the synergy between OV and Fe sites. Additionally, OV contributes to the localized surface plasmon resonance effect, enhancing the photothermal capability of the PCL/Fe-MoOv mesh. Upon near-infrared laser exposure, the catalytic activity of the PCL/Fe-MoOv mesh is further improved, leading to increased generation of reactive oxygen species and enhanced antitumor efficacy, achieving 86.7% tumor cell mortality, a 264% enhancement compared to the PCL/MoOx mesh.
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Affiliation(s)
- Wenjing Yang
- Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang 330013, China
| | - Chuanyin Zhou
- Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang 330013, China
| | - Chongxian He
- Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang 330013, China
| | - Youwen Yang
- Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang 330013, China
| | - Wurikaixi Aiyiti
- College of Mechanical Engineering, Xinjiang University, Urumqi 830017, China.
| | - Liang Xu
- Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang 330013, China.
| | - Cijun Shuai
- Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang 330013, China; State Key Laboratory of Precision Manufacturing for Extreme Service Performance, College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China.
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Huang L, Xie Y, Jiang S, Liu K, Ming Z, Shan H. Elucidating the role of pyrimidine metabolism in prostate cancer and its therapeutic implications. Sci Rep 2025; 15:2003. [PMID: 39814835 PMCID: PMC11735813 DOI: 10.1038/s41598-025-86052-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 01/07/2025] [Indexed: 01/18/2025] Open
Abstract
Our study aims to investigate the role of pyrimidine metabolism in prostate cancer and its associations with the immune microenvironment, drug sensitivity, and tumor mutation burden. Through transcriptomic and single-cell RNA sequencing analyses, we explored metabolic pathway enrichment, immune infiltration patterns, and differential gene expression in prostate cancer samples. The results showed that pyrimidine metabolism-related genes were significantly upregulated in the P2 subgroup compared to the P1 subgroup, with enhanced metabolic activity observed in basal and luminal epithelial cells. In addition, immune infiltration analysis revealed a strong correlation between pyrimidine metabolism and immune cell regulation, particularly involving T cell activity. Tumors in the P2 subgroup, characterized by higher pyrimidine metabolism, exhibited greater infiltration of activated CD4 + T cells and M2 macrophages, indicating a potential link between metabolic reprogramming and the immune response in prostate cancer. Drug sensitivity analysis further demonstrated that tumors with elevated pyrimidine metabolism displayed increased responsiveness to several chemotherapeutic agents, including BI-2536, JW-7-24-1, and PAC-1, suggesting that targeting pyrimidine metabolism may enhance treatment efficacy. Moreover, key genes involved in pyrimidine de novo synthesis, such as RRM2, were identified as potential drivers of tumor progression, providing new insights into the molecular mechanisms underlying aggressive prostate cancer phenotypes. In conclusion, pyrimidine metabolism plays a critical role in prostate cancer progression, influencing immune infiltration and drug sensitivity. Targeting this metabolic pathway offers a promising strategy for the development of new therapeutic approaches, particularly for overcoming drug resistance and improving outcomes in patients with advanced prostate cancer.
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Affiliation(s)
- Liang Huang
- Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, Hunan, China
| | - Yu Xie
- Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, Hunan, China
| | - Shusuan Jiang
- Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, Hunan, China
| | - Kan Liu
- Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, Hunan, China
| | - Zhihao Ming
- Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, Hunan, China
| | - Hong Shan
- Department of Emergency Medicine, Hengyang Medical School, The Affiliated Changsha Central Hospital, University of South China, Changsha, Hunan, China.
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Liu J, Liu J, Liang Y, Yang J, Lin Y, Li Y. Microneedle-Based Electrochemical Array Patch for Ultra-Antifouling and Ultra-Anti-Interference Monitoring of Subcutaneous Oxygen. Anal Chem 2025; 97:373-381. [PMID: 39703184 DOI: 10.1021/acs.analchem.4c04345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2024]
Abstract
Oxygen saturation is a crucial indicator in the management of various diseases and in preoperative diagnosis, and the detection of oxygen content is valuable in guiding clinical treatment. However, as the classical and dominant oxygen detection strategies, current photoelectric oximeters and electrochemical-based blood gas analyzers often suffer from significant interindividual variation and poor compliance, respectively. In recent years, wearable microneedles (MNs) for analyzing biomarkers in interstitial fluid (ISF) have received great attention and recognition mainly for the reason that the content of the substances distributed in ISF has a better correlation with that in blood circulation compared with other body fluids such as sweat and saliva. Herein, an MN-based electrochemical array system was developed for continuous subcutaneous oxygen sensing, in which gold-modified commercial acupuncture MNs were used as the sensing units, and a tailored mini-workstation, a nonwoven fabric, and a water and air isolation membrane were integrated to fabricate a wearable array patch. Notably, a multifunctional swelling resin with good biocompatibility was adopted to decorate the MN surface as a protective layer and as an electrolyte gel. The swelling resin featured the ability to reduce epidermis secretions during the sensor array penetrating the skin and to decrease the interference of other biomolecules in ISF for oxygen assay during measurement. This proposed array patch can perform the subcutaneous oxygen analysis in the physiological range of 6-150 mmHg with high sensitivity (0.3817 μA/mmHg) and low theoretical limit of detection (5.06 mmHg). It also showed decent stability and selectivity in the presence of several kinds of exogenous and endogenous substances. Finally, the patch accomplished continual monitoring of the subcutaneous oxygen content during long-term physical exercise, showing great potential in providing warning about the hypoxia status of the human body. It could be foreseen that this high-performance patch will play an active role in respiratory disease evaluation, surgical monitoring, and public health care.
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Affiliation(s)
- Jiaxi Liu
- School of Science, Harbin Institute of Technology, Shenzhen 518055, China
| | - Jiang Liu
- Key Laboratory of Xinjiang Phytomedicine Resources for Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832000, China
| | - Yanyan Liang
- School of Science, Harbin Institute of Technology, Shenzhen 518055, China
| | - Jiao Yang
- School of Science, Harbin Institute of Technology, Shenzhen 518055, China
| | - Yongping Lin
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China
| | - Yingchun Li
- School of Science, Harbin Institute of Technology, Shenzhen 518055, China
- Key Laboratory of Xinjiang Phytomedicine Resources for Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832000, China
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Jiang J, Zhao H, Chen J, Du J, Ni W, Zheng B, Wu J, Xiao C. The association between dietary creatine intake and cancer in U.S. adults: insights from NHANES 2007-2018. Front Nutr 2025; 11:1460057. [PMID: 39867555 PMCID: PMC11757134 DOI: 10.3389/fnut.2024.1460057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Accepted: 12/26/2024] [Indexed: 01/28/2025] Open
Abstract
Background Creatine has anti-inflammatory, antioxidant, and immunomodulatory effects. However, its impact on tumors remains uncertain. Methods This study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 to investigate the relationship between dietary creatine intake and cancer in American adults. A total of 25,879 participants aged 20 years and older were included, and their medical information, dietary creatine intake, and covariates were collected. Multiple logistic regression models were used to assess the relationships between age, dietary creatine intake, and cancer risk. Restricted cubic spline (RCS) analysis explored the nonlinear relationships between dietary creatine intake, age, and cancer prevalence. Results RCS analysis revealed a linear, negative association between dietary creatine intake and cancer risk. For each standard deviation (SD) increase in dietary creatine intake, cancer risk decreased by 5% (adjusted odds ratio (OR) = 0.95, 95% CI: 0.91-0.99, p = 0.025). This negative association was strongest among males (adjusted OR = 0.93, 95% CI: 0.88-0.99, p = 0.021) and overweight participants (adjusted OR = 0.92, 95% CI: 0.84-0.99, p = 0.044). Interaction results indicated specific age group effects. Further analysis showed that higher dietary creatine intake was significantly inversely associated with cancer risk among older adults (adjusted OR = 0.86, 95% CI: 0.77-0.97, p = 0.014). RCS analysis revealed a linear, positive correlation between age and cancer risk. For each SD increase in age, cancer risk increased by 3.27 times (adjusted OR = 3.27, 95% CI: 3.07-3.48, p < 0.001). Conclusion These findings suggest that higher dietary creatine intake may reduce cancer risk in a nationally representative adult population. Further prospective studies are needed to clarify the relationship between dietary creatine intake and cancer risk.
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Affiliation(s)
- Junhui Jiang
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of General Surgery, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China
| | - Hu Zhao
- Department of General Surgery, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China
| | - Jiong Chen
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of General Surgery, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China
| | - Junhao Du
- Department of General Surgery, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China
| | - Weixiang Ni
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of General Surgery, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China
| | - Baohua Zheng
- Department of General Surgery, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China
| | - Junhong Wu
- Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, China
- Department of General Surgery, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China
| | - Chunhong Xiao
- Department of General Surgery, The 900th Hospital of Joint Logistic Support Force, PLA, Fuzhou, China
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