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Xu M, Xie P, Liu S, Gao X, Yang S, Hu Z, Zhao Y, Yi Y, Dong Q, Bruns C, Kong X, Hung MC, Ren N, Zhou C. LCAT deficiency promotes hepatocellular carcinoma progression and lenvatinib resistance by promoting triglyceride catabolism and fatty acid oxidation. Cancer Lett 2025; 612:217469. [PMID: 39842501 DOI: 10.1016/j.canlet.2025.217469] [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: 09/22/2024] [Revised: 01/12/2025] [Accepted: 01/15/2025] [Indexed: 01/24/2025]
Abstract
Lecithin cholesterol acyltransferase (LCAT), a crucial enzyme in lipid metabolism, plays important yet poorly understood roles in tumours, especially in hepatocellular carcinoma (HCC). In this study, our investigation revealed that LCAT is a key downregulated metabolic gene and an independent risk factor for poor prognosis in patients with HCC. Functional experiments showed that LCAT inhibited HCC cell proliferation, migration and invasion. Mechanistically, LCAT interacts with caveolin-1 (CAV1) to promote the binding of CAV1 to PRKACA and inhibit its phosphorylation, thereby inhibiting triglyceride (TAG) catabolism. On the other hand, LCAT inhibits fatty acid oxidation (FAO) by interacting with CPT1A to promote its ubiquitination and degradation. These events result in an inadequate supply of raw materials and energy and inhibit the malignant behaviours of HCC cells. In addition, LCAT is a reliable predictive biomarker for the efficacy of lenvatinib treatment in HCC patients, and the inhibition of FAO can increase lenvatinib sensitivity in patients with LCATlow HCC. This study revealed that LCAT plays a critical role in the regulation of lipid metabolic reprogramming and is a reliable predictive biomarker for the efficacy of lenvatinib treatment in HCC patients.
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Affiliation(s)
- Min Xu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China
| | - Peiyi Xie
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China
| | - Shaoqing Liu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China; Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450001, P.R. China
| | - Xukang Gao
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China
| | - Shiguang Yang
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, PR China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, PR China; Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, 201199, PR China
| | - Zhiqiu Hu
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, PR China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, PR China; Department of Hepatobiliary and Pancreatic Surgery, Minhang Hospital, Fudan University, Shanghai, 201199, PR China
| | - Yue Zhao
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Kerpener Straße 62, 50937, Cologne, Germany
| | - Yong Yi
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China
| | - Qiongzhu Dong
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer of Shanghai Municipal Health Commission, Shanghai, 201199, PR China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai, 201199, PR China
| | - Christiane Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Kerpener Straße 62, 50937, Cologne, Germany
| | - Xiaoni Kong
- Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China.
| | - Mien-Chie Hung
- Graduate Institute of Biomedical Sciences, Institute of Biochemistry and Molecular Biology, Research Center for Cancer Biology, Cancer Biology and Precision Therapeutics Center, and Center for Molecular Medicine, China Medical University, Taichung, 40402, Taiwan.
| | - Ning Ren
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China.
| | - Chenhao Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, PR China.
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Lu W, Aihaiti A, Abudukeranmu P, Liu Y, Gao H. Arachidonic acid metabolism as a novel pathogenic factor in gastrointestinal cancers. Mol Cell Biochem 2025; 480:1225-1239. [PMID: 38963615 DOI: 10.1007/s11010-024-05057-2] [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: 05/27/2024] [Accepted: 06/25/2024] [Indexed: 07/05/2024]
Abstract
Gastrointestinal (GI) cancers are a major global health burden, representing 20% of all cancer diagnoses and 22.5% of global cancer-related deaths. Their aggressive nature and resistance to treatment pose a significant challenge, with late-stage survival rates below 15% at five years. Therefore, there is an urgent need to delve deeper into the mechanisms of gastrointestinal cancer progression and optimize treatment strategies. Increasing evidence highlights the active involvement of abnormal arachidonic acid (AA) metabolism in various cancers. AA is a fatty acid mainly metabolized into diverse bioactive compounds by three enzymes: cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. Abnormal AA metabolism and altered levels of its metabolites may play a pivotal role in the development of GI cancers. However, the underlying mechanisms remain unclear. This review highlights a unique perspective by focusing on the abnormal metabolism of AA and its involvement in GI cancers. We summarize the latest advancements in understanding AA metabolism in GI cancers, outlining changes in AA levels and their potential role in liver, colorectal, pancreatic, esophageal, gastric, and gallbladder cancers. Moreover, we also explore the potential of targeting abnormal AA metabolism for future therapies, considering the current need to explore AA metabolism in GI cancers and outlining promising avenues for further research. Ultimately, such investigations aim to improve treatment options for patients with GI cancers and pave the way for better cancer management in this area.
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Affiliation(s)
- Weiqin Lu
- General Surgery, Cancer Center, Department of Vascular Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | | | | | - Yajun Liu
- Aksu First People's Hospital, Xinjiang, China
| | - Huihui Gao
- Cancer Center, Department of Hospital Infection Management and Preventive Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
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3
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Xu S, Yin R, Zhu H, Gong Y, Zhu J, Li C, Xu Q. The role of exercise-based prehabilitation in enhancing surgical outcomes for patients with digestive system cancers: a meta-analysis. BMC Gastroenterol 2025; 25:26. [PMID: 39844027 PMCID: PMC11753026 DOI: 10.1186/s12876-025-03626-3] [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: 05/11/2024] [Accepted: 01/16/2025] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND Prehabilitation is a crucial component of tumor rehabilitation that attempts to improve patients' preoperative health, although its efficacy in treating patients with cancers of the digestive system is still up for debate. METHODS The records from PubMed (MEDLINE), Embase, Web of Science, Cochrane Library, EBSCO, Scopus, CNKI and Wan fang database up to November 2024 were systematically searched. The Cochrane Collaboration tool was employed for evaluating the risk of bias in each study, and the PRISMA 2020 checklist provided by the EQUATOR network was utilized. RESULTS Through quality analysis, 20 articles were included, involving 1719 patients. Although its effect on severe complications is still unknown, the prehabilitation significantly decreased overall postoperative complications when compared to standard care, with a risk ratio (RR) of 0.74 (95% CI: 0.65 to 0.84). Despite not shortening the postoperative hospital stay (MD: -0.13, 95% CI: -0.29 to 0.03), prehabilitation demonstrated notable improvements in the 6-minute walk distance (6MWD), with preoperative gains (MD: 25.87, 95% CI: 14.49 to 37.25) and sustained benefits at 4 weeks postoperatively (MD: 22.48, 95% CI: 7.85 to 37.12). However, no significant differences in 6MWD were observed at 6 or 8 weeks postoperatively. The average improvement in 6MWD from baseline to preoperative was 28.99 (95% CI: 10.89 to 47.08, P = 0.002), and from 4 weeks postoperative to baseline, it was 25.95 (95% CI: 6.84 to 45.07, P = 0.008), with no significant change at 8 weeks. The acceptance and completion rates of prehabilitation were commendably high at 61% (95% CI: 47-75%) and 90% (95% CI: 87-93%), respectively, alongside a relatively low dropout rate of 10% (95% CI: 7% to13%). CONCLUSIONS Prehabilitation reduces postoperative complications and improves short-term physical function in digestive surgery patients, with good patient acceptance; however, the long-term effects are unknown due to a lack of follow-up data. REGISTRATION It was registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the identification code CRD42022361100.
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Affiliation(s)
- Shasha Xu
- Department of Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Gulou District, Nanjing, 210000, Jiangsu Province, China
| | - Rong Yin
- Department of Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Gulou District, Nanjing, 210000, Jiangsu Province, China
| | - Haiou Zhu
- Department of Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Gulou District, Nanjing, 210000, Jiangsu Province, China
| | - Yin Gong
- Department of Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Gulou District, Nanjing, 210000, Jiangsu Province, China
| | - Jing Zhu
- Department of Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Gulou District, Nanjing, 210000, Jiangsu Province, China
| | - Changxian Li
- Department of Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Gulou District, Nanjing, 210000, Jiangsu Province, China
| | - Qin Xu
- Department of Nursing School, Nanjing Medical University, Nanjing, 210000, Jiangsu Province, China.
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Chen X, Gong R, Wang L, Lei K, Liu X, Wang J, Sun M, Saluja AK, Yu Q, Ren H. hnRNPLL regulates MYOF alternative splicing and correlates with early metastasis in pancreatic ductal adenocarcinoma. Cancer Lett 2024; 611:217436. [PMID: 39742990 DOI: 10.1016/j.canlet.2024.217436] [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: 10/01/2024] [Revised: 11/30/2024] [Accepted: 12/29/2024] [Indexed: 01/04/2025]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer known for its high rate of early metastasis, necessitating the discovery of the underlying mechanisms. Herein, we report that heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) expression significantly increases at the invasion forefront in PDAC and is associated with early metastasis and poor prognosis. Our findings revealed that hnRNPLL knockdown resulted in extensive exon skipping (ES) events. In particular, we identified myoferlin (MYOF), a member of the ferlin family involved in membrane processes, as a functional splicing target of hnRNPLL. hnRNPLL depletion stimulates MYOF exon 17 retention to reduce the short isoform of MYOF (MYOFb) and inhibit metastasis. In contrast, hnRNPLL or MYOFb overexpression promoted pancreatic cancer cell migration and invasion. These results suggest that hnRNPLL is a critical factor for early PDAC metastasis. hnRNPLL and MYOFb may be potential therapeutic targets for PDAC.
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Affiliation(s)
- Xianghan Chen
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University (Air Force Medical University), Xi'an, 710032, China
| | - Ruining Gong
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; Gastrointestinal Cancer Institute/Pancreatic Disease Institute, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Lili Wang
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Ke Lei
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Xiaolan Liu
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Jigang Wang
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Mingyue Sun
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Ashok Kumar Saluja
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Qian Yu
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
| | - He Ren
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; Gastrointestinal Cancer Institute/Pancreatic Disease Institute, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
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5
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Tao Z, Chen Z, Zeng X, Cui J, Quan M. An emerging aspect of cancer neuroscience: A literature review on chemotherapy-induced peripheral neuropathy. Cancer Lett 2024; 611:217433. [PMID: 39736454 DOI: 10.1016/j.canlet.2024.217433] [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: 09/03/2024] [Revised: 12/20/2024] [Accepted: 12/24/2024] [Indexed: 01/01/2025]
Abstract
The nervous system governs both ontogeny and oncology. Foundational discoveries have clarified the direct communication of neurotransmitters with tumors and indirect interactions through neural effects on the immune system and the tumor microenvironment. Meantime, the nervous system is susceptible to cancer and its treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is the most common side effects that significantly reduce the efficacy of anti-cancer treatment and patients' quality of life by leading to dose reduction or early cessation of chemotherapy. However, there are no effective strategies to reverse or treat CIPN. A better understanding of the mechanisms is expected to enable the development of the next generation of therapies. Here, we summarize the recent important studies on clinical manifestations, risk factors, prediction, pathogenesis, prevention, and treatment of CIPN. We also provide perspectives and insights regarding the rationales of bidirectional interactions between cancer and the nervous system.
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Affiliation(s)
- Zhirui Tao
- Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China
| | - Zhiqin Chen
- Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China
| | - Xiaochen Zeng
- Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China
| | - Jiujie Cui
- Department of Oncology and State Key Laboratory of Systems Medicine for Cancer of Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
| | - Ming Quan
- Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China.
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6
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Xu C, Jiang C, Tian Y, Liu Y, Zhang H, Xiang Z, Xue H, Gu L, Xu Q. Nervous system in colorectal cancer. Cancer Lett 2024; 611:217431. [PMID: 39725147 DOI: 10.1016/j.canlet.2024.217431] [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] [Revised: 11/28/2024] [Accepted: 12/24/2024] [Indexed: 12/28/2024]
Abstract
A malignant tumor is a complex systemic disease involving the nervous system, which regulates nerve signals. Cancer neuroscience is a field that explores the interactions between tumors and the nervous system. The gastrointestinal tract is a typical peripheral organ with abundant neuroregulation and is regulated by the peripheral, enteric, and central nervous systems (PNS, ENS, and CNS, respectively). The physiological functions of the gastrointestinal tract are maintained via complex neuromodulation. Neuroregulatory imbalance is the primary cause of gastrointestinal diseases, including colorectal cancer (CRC). In CRC, there is a direct interaction between the nervous system and tumor cells. Moreover, this tumor-nerve interaction can indirectly regulate the tumor microenvironment, including the microbiota, immunity, and metabolism. In addition to the lower nerve centers, the stress response, emotion, and cognition represented by the higher nerve centers also participate in the occurrence and progression of CRC. Herein, we review some basic knowledge regarding cancer neuroscience and elucidate the mechanism underlying tumor-nerve interactions in CRC.
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Affiliation(s)
- Chunjie Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China
| | - Chunhui Jiang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China
| | - Yuan Tian
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China
| | - Ye Liu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China
| | - Hao Zhang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China
| | - Zeyu Xiang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China
| | - Hanbing Xue
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, China.
| | - Lei Gu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China.
| | - Qing Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, China.
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7
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Li D, Chu X, Ma Y, Zhang F, Tian X, Yang Y, Yang Y. Tumor-derived exosomes: Unravelling the pathogenesis of pancreatic cancer with liver metastases and exploring the potential for clinical translation. Cancer Lett 2024; 611:217403. [PMID: 39709178 DOI: 10.1016/j.canlet.2024.217403] [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: 07/21/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
Pancreatic cancer (PC) is one of the most malignant solid cancers, and PC metastasis, particularly liver metastasis, is a major cause of cancer mortality. A key event in tumor metastasis is the formation of pre-metastatic niche (PMN), which provides a microenvironment conducive to tumor cells colonization and progression. Various molecules loaded in tumor-derived exosomes (TDEs) contribute to PMN formation and distant tumor metastasis, by regulating immune and stromal cell function, inducing angiogenesis, and promoting metabolic reprogramming. Therefore, therapies targeting PMN may offer novel advantages to prevent tumor metastasis at an earlier stage. In this review, we summarize multifaceted mechanisms underlying hepatic PMN formation, with a focus on how PC TDEs participate in angiogenesis and vascular permeability, create immune suppressive microenvironment, remodel the extracellular matrix, and regulate metabolic reprogramming. In addition, we highlight the promise of TDEs for early diagnosis and effective therapy of PC liver metastases.
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Affiliation(s)
- Dongqi Li
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Xiangyu Chu
- Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, State Key Lab of Digestive Health, National Clinical Research Center for Digestive Diseases, Beijing, China
| | - Yongsu Ma
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Fusheng Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, 100034, China
| | - Xiaodong Tian
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, 100034, China.
| | - Yanlian Yang
- CAS Key Laboratory of Biological Effects of Nanomaterials and Nanosafety, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, China.
| | - Yinmo Yang
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, 100034, China.
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8
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Yuan J, Lu J, Zhu J, Chen F, Zeng Z, Yan J, Li Q, Zhou R, Tong Q. LncRNA FIRRE drives gastric cancer progression via ZFP64-mediated TUBB3 promoter activation. Cancer Lett 2024; 611:217398. [PMID: 39706253 DOI: 10.1016/j.canlet.2024.217398] [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: 06/05/2024] [Revised: 12/10/2024] [Accepted: 12/14/2024] [Indexed: 12/23/2024]
Abstract
Gastric cancer is a common global malignancy that requires detailed study of its development mechanisms. Although LncRNA FIRRE is known to play a crucial role in the progression and treatment resistance of several cancers, its effect on gastric cancer is not well understood. This study confirms the impact of FIRRE on the malignant behavior of gastric cancer. Using RNA-sequencing, dual luciferase reporter assay, RIP and CHIP, we identified transcription factors and target genes linked to FIRRE. Elevated FIRRE expression in gastric cancer correlates with worse patient prognosis and promotes gastric cancer proliferation, migration, and invasion both in vitro and in vivo. FIRRE regulates the TUBB3 gene, facilitating gastric cancer progression by activating the TUBB3 promoter in vitro. ZFP64 is the transcription factor for TUBB3, activating its promoter and binding specifically with FIRRE. Reducing ZFP64 disrupts FIRRE's positive regulation of TUBB3 in vitro and in vivo. This study shows FIRRE promotes gastric cancer progression by binding to ZFP64 and activating the TUBB3 promoter.
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Affiliation(s)
- Jingwen Yuan
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan, 430060, China; Colorectal Surgery Department, Changhai Hospital, Naval Medical University, Shanghai, 200433, China
| | - Jiatong Lu
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Jie Zhu
- Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Parasitology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China
| | - Fangfang Chen
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Zhi Zeng
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Junfeng Yan
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Qiang Li
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Rui Zhou
- Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Parasitology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, China.
| | - Qiang Tong
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
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9
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Liu Y, Gu X, Xuan M, Lou N, Fu L, Li J, Xue C. Notch signaling in digestive system cancers: Roles and therapeutic prospects. Cell Signal 2024; 124:111476. [PMID: 39428027 DOI: 10.1016/j.cellsig.2024.111476] [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: 08/29/2024] [Revised: 09/20/2024] [Accepted: 10/17/2024] [Indexed: 10/22/2024]
Abstract
Digestive system cancers rank among the most prevalent malignant tumors, maintaining persistently high incidence and mortality rates. Notch signaling activity, often aberrant in esophageal, gastric, hepatic, pancreatic, and colorectal cancers, plays a pivotal role in the initiation, progression, and therapy resistance of these malignancies. As a highly conserved pathway, Notch signaling is integral to cell differentiation, survival, proliferation, stem cell renewal, development, and morphogenesis. Its dysregulation has been increasingly linked to various diseases, particularly digestive system cancers. In these malignancies, altered Notch signaling influences multiple biological processes, including cell proliferation, invasion, cell cycle progression, immune evasion, drug resistance, and stemness maintenance. Understanding the mechanisms of Notch signaling in digestive system cancers is essential for the development of novel targeted therapies. Numerous Notch pathway-targeting drugs are currently in preclinical studies, demonstrating promising efficacy both as monotherapies and in combination with conventional anti-cancer treatments. This review summarizes recent high-quality findings on the involvement of Notch signaling in digestive system cancers, focusing on the expression changes and pathological mechanisms of its dysregulated components. Special emphasis is placed on the potential of translating Notch-targeted approaches into therapeutic strategies, which hold promise for overcoming the limitations of existing treatments and improving the poor prognosis associated with these cancers.
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Affiliation(s)
- Yingru Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Xinyu Gu
- Department of Oncology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan 471000, China
| | - Mengjuan Xuan
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Na Lou
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Leiya Fu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
| | - Juan Li
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
| | - Chen Xue
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
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10
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Li ZZ, Zhou K, Wu Q, Liu B, Bu LL. Lymph node metastasis in cancer: Clearing the clouds to see the dawn. Crit Rev Oncol Hematol 2024; 204:104536. [PMID: 39426554 DOI: 10.1016/j.critrevonc.2024.104536] [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: 05/22/2024] [Revised: 09/26/2024] [Accepted: 10/06/2024] [Indexed: 10/21/2024] Open
Abstract
Lymph node metastasis (LNM) is often regarded as an indicator of poor prognosis in various cancers. Despite over three centuries of exploration since its discovery, the molecular mechanisms underlying LNM remain inconclusive. This review summarizes the molecular mechanisms of LNM, using the "PUMP+" principle for clarification. Pathological examination remains the gold standard for LNM diagnosis, yet there is a need to explore early diagnostic strategies that can effectively improve patient outcomes. With the advent of immunotherapy, discussions on the fate of lymph nodes (LN) have emerged, emphasizing the importance of preserving LN integrity prior to immunotherapy. This, in turn, poses higher demands for diagnostic accuracy and precision treatment of LNM. This review comprehensively discusses the molecular mechanisms, diagnostic methods, and treatment strategies for cancer lymph node metastasis, along with current bottlenecks and future directions in this field.
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Affiliation(s)
- Zi-Zhan Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China
| | - Kan Zhou
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China
| | - Qiuji Wu
- Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan China
| | - Bing Liu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Department of Oral & Maxillofacial - Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
| | - Lin-Lin Bu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China; Department of Oral & Maxillofacial - Head Neck Oncology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
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11
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Tang Y, Shi T, Lin S, Fang T. Current status of research on the mechanisms of tumor-associated macrophages in esophageal cancer progression. Front Oncol 2024; 14:1450603. [PMID: 39678502 PMCID: PMC11638059 DOI: 10.3389/fonc.2024.1450603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 09/27/2024] [Indexed: 12/17/2024] Open
Abstract
Esophageal carcinoma (EC) is one of the most common tumors in China and seriously affects patient survival and quality of life. In recent years, increasing studies have shown that the tumor microenvironment is crucial in promoting tumor progression and metastasis. Tumor-associated macrophages (TAM) are key components of the tumor immune microenvironment and promote both tumor growth and antitumor immunity. Much evidence suggests that TAMs are closely associated with esophageal tumors. However, understanding of the clinical value and mechanism of action of TAM in esophageal cancer remains limited. Therefore, we reviewed the status of research on the role and mechanism of action of TAM in EC progression and summarized its potential clinical application value to provide a theoretical basis for the clinical treatment of EC.
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Affiliation(s)
- Yuchao Tang
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Tingting Shi
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
| | - Shu Lin
- Centre of Neurological and Metabolic Research, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
- Group of Neuroendocrinology, Garvan Institute of Medical Research, Sydney, Australia
| | - Taiyong Fang
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China
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12
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Xue Y, Zhang Y, Su Y, Zhao J, Yu D, Jo Y, Joo J, Lee HJ, Ryu D, Wei S. The implicated role of GDF15 in gastrointestinal cancer. Eur J Clin Invest 2024; 54:e14290. [PMID: 39044314 DOI: 10.1111/eci.14290] [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: 04/26/2024] [Accepted: 07/03/2024] [Indexed: 07/25/2024]
Abstract
BACKGROUND Growth differentiation factor 15 (GDF15), a stress-responsive cytokine from transforming growth factor superfamily, is highly expressed in mammalian tissues, including pancreas, stomach and intestine under pathological conditions. In particular, elevated levels of GDF15 might play an important role in the development and progression of various gastrointestinal cancers (GCs), suggesting its potential as a promising target for disease prediction and treatment. METHODS In this review, systematic reviews addressing the role of GDF15 in GCs were updated, along with the latest clinical trials focussing on the GDF15-associated digestive malignancies. RESULTS The multiple cellular pathways through which GDF15 is involved in the regulation of physiological and pathological conditions were first summarized. Then, GDF15 was also established as a valuable clinical index, functioning as a predictive marker in diverse GCs. Notably, latest clinical treatments targeting GDF15 were also highlighted, demonstrating its promising potential in mitigating and curing digestive malignancies. CONCLUSIONS This review unveils the pivotal roles of GDF15 and its potential as a promising target in the pathogenesis of GCs, which may provide insightful directions for future investigations.
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Affiliation(s)
- Yingqi Xue
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
| | - Yan Zhang
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
- Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
| | - Yale Su
- Department of Cardiovascular Surgery, The Second Hospital of Jilin University, Changchun, China
| | - Jiangqi Zhao
- Department of Dermatology, The Second Hospital of Jilin University, Changchun, China
| | - Daoquan Yu
- Department of Hepatological Surgery, Shuangliao Center Hospital, Shuangliao, China
| | - Yunju Jo
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
| | - Jongkil Joo
- Department of Obstetrics and Gynecology, Pusan National University Hospital, Busan, Korea
| | - Hyun Joo Lee
- Department of Obstetrics and Gynecology, Pusan National University Hospital, Busan, Korea
| | - Dongryeol Ryu
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
| | - Shibo Wei
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
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13
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Dong Y, Fan ZZ, Li WT, Kang J, Zhang Y, Guan Y, Xu HQ, Yuan J, Xu F. Burden of gastrointestinal cancers among working-age population over past thirty years in China. World J Gastrointest Oncol 2024; 16:3955-3979. [PMID: 39350983 PMCID: PMC11438773 DOI: 10.4251/wjgo.v16.i9.3955] [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: 06/27/2024] [Revised: 07/15/2024] [Accepted: 08/07/2024] [Indexed: 09/09/2024] Open
Abstract
BACKGROUND Although gastrointestinal (GI) cancers have been becoming a great public health concern in China, there is currently a lack of comprehensive literature on the overall burden and changing trends of GI cancers in the working-age population. AIM To assess the burden of GI cancers and to examine the overall, age- and gender-specific trends among the working-age population in China from 1990 to 2019. METHODS Data were extracted from the Global Burden of Disease Study 2019. The burden of GI cancers was indicated by incidence, mortality, disability-adjusted life-years (DALYs), age-standardized incidence rate (ASIR), age-standardized mortality rate, and age-standardized DALYs rate. Trends in the burden of GI cancers from 1990 to 2019 were examined using annual percent change and average annual percent change with Joinpoint regression models. RESULTS For overall GI cancers, a declining trend was observed in the ASIR, age-standardized mortality rate, and age-standardized DALYs rate, with reductions of 0.74%, 2.23%, and 2.22%, respectively, from 1999 to 2019 in the Chinese working-age population. However, an increasing trend was observed in the ASIR for overall GI cancers from 2016-2019. The number of either incident cases, mortality cases, and DALYs was higher for colon/rectum cancer and liver cancer in younger participants but lower for esophageal, gallbladder, biliary tract, pancreatic, and stomach cancer among older subjects. Moreover, sex disparity in the GI cancers burden was also examined over 30 years. CONCLUSION The total burden of GI cancers remained heavy among the working-age population in China, although declining trends were observed from 1999 to 2019. Disparities in the GI cancers burden existed between sexes, age groups, and cancer types. Population-based precision prevention strategies are needed to tackle GI cancers among working-age individuals, considering the age, sex, and cancer type disparities in China.
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Affiliation(s)
- Yu Dong
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
| | - Zhuan-Zhuan Fan
- Department of Primary Healthcare Management, Nanjing Municipal Center for Disease Control and Prevention, Nanjing 210003, Jiangsu Province, China
| | - Wen-Ting Li
- Department of Primary Healthcare Management, Nanjing Municipal Center for Disease Control and Prevention, Nanjing 210003, Jiangsu Province, China
| | - Jian Kang
- Department of Emergency, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Yan Zhang
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
| | - Yue Guan
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
| | - Hui-Qing Xu
- Department of Epidemiology, Nanjing Medical University School of Public Health, Nanjing 211116, Jiangsu Province, China
| | - Jie Yuan
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
| | - Fei Xu
- Department of Primary Healthcare Management, Nanjing Municipal Center for Disease Control and Prevention, Nanjing 210003, Jiangsu Province, China
- Department of Epidemiology, Nanjing Medical University School of Public Health, Nanjing 211116, Jiangsu Province, China
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14
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Liu H, Xu Z, Song C, Lu Y, Li T, Zheng Z, Li M, Ye H, Wang K, Shi J, Wang P. Burden of gastrointestinal cancers among people younger than 50 years in China, 1990 to 2019. Public Health 2024; 234:112-119. [PMID: 38972229 DOI: 10.1016/j.puhe.2024.06.008] [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: 02/19/2024] [Revised: 05/13/2024] [Accepted: 06/07/2024] [Indexed: 07/09/2024]
Abstract
OBJECTIVES This study aimed to assess the burden of early-onset gastrointestinal (GI) cancers in China over three decades. STUDY DESIGN A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS Data on early-onset GI cancers in 2020 and from 1990 to 2019 were extracted from GLOBOCAN 2020 database and GBD 2019, respectively. The average annual percent change (AAPC) was calculated to analyze the temporal trends using the Joinpoint Regression Program. The Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2030. RESULTS In China, there were 185,980 incident cases and 119,116 deaths of early-onset GI cancer in 2020, with the highest incidence and mortality observed in liver cancer (new cases: 71,662; deaths: 62,412). The spectrum of early-onset GI cancers in China has transitioned over the last 30 years. The age-standardized rates of incidence, mortality, and disability-adjusted life years for colorectal and pancreatic cancers exhibited rapid increases (AAPC >0, P ≤ 0.001). The fastest-growing incidence rate was found in colorectal cancer (AAPC: 3.06, P < 0.001). Despite the decreases in liver, gastric, and esophageal cancers, these trends have been reversed or flattened in recent years. High body mass index was found to be the fastest-growing risk factor for early-onset GI cancers (estimated annual percentage change: 2.75-4.19, P < 0.05). Projection analyses showed an increasing trend in age-standardized incidence rates for almost all early-onset GI cancers during 2020-2030. CONCLUSIONS The transitioning pattern of early-onset GI cancers in China emphasizes the urgency of addressing this public health challenge.
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Affiliation(s)
- H Liu
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - Z Xu
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
| | - C Song
- The Institution for Chronic and Noncommunicable Disease Control and Prevention, Zhengzhou Center for Disease Control and Prevention, Zhengzhou, 450052, Henan Province, China
| | - Y Lu
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - T Li
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - Z Zheng
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - M Li
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - H Ye
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - K Wang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - J Shi
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - P Wang
- Department of Epidemiology and Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China; Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
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Zou S, Zhang L, Jiang C, Li F, Yang Y, Deng X, Zhang J, Chen H, Jiang L, Cheng X, Deng L, Lin L, Shen B, Wen C, Zhan Q. Driver mutation subtypes involve with differentiated immunophenotypes influencing pancreatic cancer outcomes. Cancer Lett 2024; 599:217134. [PMID: 39094824 DOI: 10.1016/j.canlet.2024.217134] [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: 04/10/2024] [Revised: 07/03/2024] [Accepted: 07/23/2024] [Indexed: 08/04/2024]
Abstract
Despite many studies focusing on the prognostic biomarkers in pancreatic adenocarcinomas (PAADs), there is ill-informed about the relationships between their genomic features and immune characteristics. Herein, we deeply investigated the involvement of major driver mutation subtypes with immunophenotypes impacting PAAD outcomes. Based on public data analyses of RNA expression-based immune subtypes in PAAD, in contrast to KRAS G12D & TP53 co-mutant patients with poor outcomes, the best immune subtype C3 (inflammatory) characterized by high Th1/Th2 ratio was relatively enriched in KRASnon-G12DTP53wt patients with better survival, whereas the inferior subtype C2 (IFN-γ dominant) with low Th1/Th2 ratio was more common in the former than in the latter. Moreover, contrary to the highly immunosuppressive microenvironment (high Treg, high ratio of Treg to tumor-specific CD4+ T cell) in KRASG12DTP53mut patients, KRASG12VTP53wt individuals exhibited an inflamed context profiled by multiplex immunohistochemistry. It could be responsible for their outstanding survival advantage over others in postsurgical PAAD patients receiving adjuvant chemotherapy as shown by our cohort. Together, KRASG12VTP53wt may be a promising biomarker for prognostic evaluation and screening certain candidates with PAAD to get desirable survival benefit from adjuvant chemotherapy.
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Affiliation(s)
- Siyi Zou
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, PR China
| | - Lei Zhang
- Genecast Biotechnology Co., Ltd, 88 Danshan Road, Xidong Chuangrong Building, Suite C 1310-1318, Xishan District, Wuxi City, Jiangsu, 214104, PR China
| | - Cen Jiang
- Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China
| | - Fanlu Li
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, PR China
| | - Ying Yang
- Genecast Biotechnology Co., Ltd, 88 Danshan Road, Xidong Chuangrong Building, Suite C 1310-1318, Xishan District, Wuxi City, Jiangsu, 214104, PR China
| | - Xiaxing Deng
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, PR China
| | - Jiao Zhang
- Genecast Biotechnology Co., Ltd, 88 Danshan Road, Xidong Chuangrong Building, Suite C 1310-1318, Xishan District, Wuxi City, Jiangsu, 214104, PR China
| | - Hao Chen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, PR China
| | - Lingxi Jiang
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, PR China
| | - Xueyan Cheng
- Genecast Biotechnology Co., Ltd, 88 Danshan Road, Xidong Chuangrong Building, Suite C 1310-1318, Xishan District, Wuxi City, Jiangsu, 214104, PR China
| | - Lisha Deng
- Genecast Biotechnology Co., Ltd, 88 Danshan Road, Xidong Chuangrong Building, Suite C 1310-1318, Xishan District, Wuxi City, Jiangsu, 214104, PR China
| | - Lin Lin
- Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China.
| | - Baiyong Shen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
| | - Chenlei Wen
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
| | - Qian Zhan
- Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 200025, PR China; Research Institute of Pancreatic Diseases, Shanghai Key Laboratory of Translational Research for Pancreatic Neoplasms, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, PR China.
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Zhao S, Yin G, Zhao M, Wu J, Liu X, Wei L, Xu Q, Xu J. Inflammation as a pathway for heavy metal-induced liver damage-Insights from a repeated-measures study in residents exposed to metals and bioinformatics analysis. Int J Hyg Environ Health 2024; 261:114417. [PMID: 38968837 DOI: 10.1016/j.ijheh.2024.114417] [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: 04/02/2024] [Revised: 06/08/2024] [Accepted: 06/27/2024] [Indexed: 07/07/2024]
Abstract
BACKGROUND Epidemiological studies on heavy metal exposure and liver injury are predominantly cross-sectional, lacking longitudinal data and exploration of potential mechanisms. METHOD We conducted a repeated-measures study in Northeast China from 2016 to 2019, involving 322 participants. Linear mixed models (LMM) and Bayesian kernel machine regression (BKMR) were employed to explore the associations between individual and mixed blood metal concentrations [chromium (Cr), cadmium (Cd), vanadium (V), manganese (Mn), lead (Pb)] and liver function biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), globulin (GLB), total protein (TP)]. Mediation and enrichment analyses were used to determine whether the inflammatory response is a critical pathway for heavy metal-induced liver damage. RESULT We obtained a total of 958 observations. The results from LMM and BKMR indicated significant associations between individual and mixed heavy metals and liver function biomarkers. Longitudinal analysis revealed associations between Cd and the annual increase rate of ALT (β = 2.61; 95% CI: 0.97, 4.26), the annual decrease rate of ALB (β = -0.21; 95% CI: -0.39, -0.03), Mn and the annual increase rate of GLB (β = 0.38; 95% CI: 0.05, 0.72), and V and the annual decrease rate of ALB/GLB (β = -1.15; 95% CI: -2.00, -0.31). Mediation analysis showed that high-sensitivity C-reactive protein (hsCRP) mediated the associations between Cd and AST, TP, with mediation effects of 27.7% and 13.4%, respectively. Additionally, results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses supported the role of inflammatory response pathways. CONCLUSION Our findings indicate that heavy metal exposure leads to liver damage, with the inflammatory response potentially serving as a crucial pathway in this process. This study offers a novel perspective on understanding heavy metal-induced liver injury and provides insights for preventive measures against the health damage caused by heavy metals.
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Affiliation(s)
- Shuanzheng Zhao
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Guohuan Yin
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Meiduo Zhao
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Jingtao Wu
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Xiaolin Liu
- Department of Epidemiology and Biostatistics, Jinzhou Medical University, Jinzhou, 121001, Liaoning, China
| | - Lanping Wei
- Jinzhou Central Hospital, Jinzhou, 121001, Liaoning, China
| | - Qun Xu
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China
| | - Jing Xu
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center of Environmental and Health Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China.
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17
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Lv C, Wang Y, Kong L, Guo J, Chen X, Guo F, Dong Z, Li Z, Yang X, Yang M, Yang W, Li F, Zhang H. Securinine inhibits carcinogenesis in gastric cancer by targeting AURKA-β-catenin/Akt/STAT3 and the cell cycle pathway. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 130:155735. [PMID: 38810557 DOI: 10.1016/j.phymed.2024.155735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 05/02/2024] [Accepted: 05/12/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Gastric cancer (GC) is difficult to treat with currently available treatments. Securinine (SCR) has a lengthy history of use in the treatment of disorders of the nervous system, and its anticancer potential has been gaining attention in recent years. The aim of this study was to explore the repressive effect of SCR on GC and its fundamental mechanism. METHODS The efficacy of SCR in GC cells was detected by MTT assays. Colony formation, flow cytometry and Transwell assays were used to assess the changes in the proliferation, apoptosis, cell cycle distribution, migration and invasion of GC cells after treatment. AGS (human gastric carcinoma cell)-derived xenografts were used to observe the effect of SCR on tumor growth in vivo. The molecular mechanism of action of SCR in GC was explored via RNA sequencing, bioinformatics analysis, Western blotting, molecular docking, and immunohistochemistry. RESULTS SCR was first discovered to inhibit the proliferation, migration, and invasion of GC cells while initiating apoptosis and cell cycle arrest in vitro. It was also established that SCR has excellent anticancer effects in vivo. Interestingly, AURKA acts as a crucial target of SCR, and AURKA expression can be blocked by SCR. Moreover, this study revealed that SCR suppresses the cell cycle and the β-catenin/Akt/STAT3 pathways, which were previously reported to be regulated by AURKA. CONCLUSION SCR exerts a notable anticancer effect on GC by targeting AURKA and blocking the cell cycle and β-catenin/Akt/STAT3 pathway. Thus, SCR is a promising pharmacological option for the treatment of GC.
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Affiliation(s)
- Caixia Lv
- Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University/Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, PR China; The Second Clinical Medical College, Shanxi Medical University, Taiyuan, PR China
| | - Yun Wang
- The Second Clinical Medical College, Shanxi Medical University, Taiyuan, PR China; Department of Orthopedics, The Second People's Hospital of Changzhi, Changzhi, PR China
| | - Luke Kong
- Basic Medical College, Shanxi Medical University, Taiyuan, PR China; Department of Medical Laboratory, Jincheng People's Hospital, Jincheng, PR China
| | - Jianghong Guo
- The Second Clinical Medical College, Shanxi Medical University, Taiyuan, PR China; Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, PR China
| | - Xiaoxia Chen
- Department of Medicine, Shanxi Renan Hospital, Taiyuan, PR China
| | - Fengtao Guo
- Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University/Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, PR China; The Second Clinical Medical College, Shanxi Medical University, Taiyuan, PR China
| | - Zhuanxia Dong
- Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University/Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, PR China; The Second Clinical Medical College, Shanxi Medical University, Taiyuan, PR China
| | - Zhiyuan Li
- Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University/Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, PR China; The Second Clinical Medical College, Shanxi Medical University, Taiyuan, PR China
| | - Xihua Yang
- Laboratory Animal Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, PR China
| | - Mudan Yang
- Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University/Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, PR China
| | - Wenhui Yang
- Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University/Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, PR China.
| | - Feng Li
- Central Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, PR China.
| | - Huanhu Zhang
- Department of Gastroenterology, Cancer Hospital Affiliated to Shanxi Medical University/Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, PR China; Shanxi University of Chinese Medicine, Jin Zhong, PR China.
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Peng H, Zhang Z, Wu Y, Zhu Y. Correlations of pathomorphological parameters between lesions at the invasive front and lymph node metastases in colorectal cancer: a retrospective clinical study. J Egypt Natl Canc Inst 2024; 36:23. [PMID: 38945978 DOI: 10.1186/s43046-024-00228-0] [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: 07/10/2023] [Accepted: 05/29/2024] [Indexed: 07/02/2024] Open
Abstract
BACKGROUND Lymph node (LN) metastasis is one of the most important indicators to evaluate stage, choose treatment strategy, and predict outcome of colorectal cancer (CRC). The morphological correlation between primary tumors and LN metastases can help predict the incidence of LN metastasis in CRC more accurately and assist with more individualized risk-stratification management decisions. METHODS A retrospective study was devised with paired tissue specimens from the invasive front of primary tumors and LN metastases in 426 patients after a radial surgery for CRC. According to the presence (N +) or absence (N-) of regional LN metastasis and the number of LN metastases (pN1a/1b/1c/2a/2b), comparisons were performed regarding tumor budding (TB) and poorly-differentiated clusters (PDC). In addition, their correlation with the incidence of LN metastasis and the extent were explored. RESULTS The TB and PDC in the invasive front of primary tumors presented significant correlations with the incidence of LN metastasis and the number of LN metastases in CRC (P < 0.001). TB2/3 led to a risk of LN metastasis 6.68-fold higher than TB1, while PDC2/3 resulted in a risk of LN metastasis 8.46-fold higher than PDC1. Additionally, the risk of developing 4 or more LN metastases was 3.08-fold and 2.86-fold higher upon TB2/3 and PDC2/3 than that with TB1 and PDC1, respectively. Moderate positive correlations were found between the invasive front of primary tumors and LN metastases in terms of TB and PDC, respectively. CONCLUSIONS TB and PDC, at the invasive tumor front are important morphological markers to evaluate LN metastasis in CRC, and they can be employed as reference indicators to assess or predict the potential of LN metastasis in CRC in clinical practice.
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Affiliation(s)
- Hui Peng
- Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine/Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China.
- Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, Zhuhai Hospital, Zhuhai, 519000, China.
| | - Zhifa Zhang
- Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine/Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
| | - Yingjun Wu
- Department of Pathology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine/Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China
| | - Yalan Zhu
- Department of Pathology, Guangdong Provincial Hospital of Chinese Medicine, Zhuhai Hospital, Zhuhai, 519000, China
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Chen Q, Chen J, Deng Y, Bi X, Zhao J, Zhou J, Huang Z, Cai J, Xing B, Li Y, Li K, Zhao H. Personalized prediction of postoperative complication and survival among Colorectal Liver Metastases Patients Receiving Simultaneous Resection using machine learning approaches: A multi-center study. Cancer Lett 2024; 593:216967. [PMID: 38768679 DOI: 10.1016/j.canlet.2024.216967] [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: 03/25/2024] [Revised: 05/14/2024] [Accepted: 05/15/2024] [Indexed: 05/22/2024]
Abstract
BACKGROUND To predict clinical important outcomes for colorectal liver metastases (CRLM) patients receiving colorectal resection with simultaneous liver resection by integrating demographic, clinical, laboratory, and genetic data. METHODS Random forest (RF) models were developed to predict postoperative complications and major complications (binary outcomes), as well as progression-free survival (PFS) and overall survival (OS) (time-to-event outcomes) of the CRLM patients based on data from two hospitals. The models were validated on an external dataset from an independent hospital. The clinical utility of the models was assessed via decision curve analyses (DCA). RESULTS There were 1067 patients included in survival prediction analyses and 1070 patients included in postoperative complication prediction analyses. The RF models provided an assessment of the model contributions of features for outcomes and suggested KRAS, BRAF, and MMR status were salient for the PFS or OS predictions. RF model of PFS showed that the Brier scores at 1-, 3-, and 5-year PFS were 0.213, 0.202 and 0.188; and the AUCs of 1-, 3- and 5-year PFS were 0.702, 0.720 and 0.743. RF model of OS revealed that Brier scores of 1-,3-, and 5-year OS were 0.040, 0.183 and 0.211; and the AUCs of 1-, 3- and 5-year OS were 0.737, 0.706 and 0.719. RF model for postoperative complication resulted in an AUC of 0.716 and a Brier score of 0.196. DCA curves clearly demonstrated that the RF models for these outcomes exhibited a superior net benefit across a wide range of threshold probabilities, signifying their favorable clinical utility. The RF models consistently exhibited robust performance in both internal cross-validation and external validation. The individualized risk profile predicted by the models closely aligned with the actual survival outcomes observed for the patients. A web-based tool (https://kanli.shinyapps.io/CRLMRF/) was provided to demonstrate the practical use of the prediction models for new patients in the clinical setting. CONCLUSION The predictive models and a web-based tool for personalized prediction demonstrated a moderate predictive performance and favorable clinical utilities on several key clinical outcomes of CRLM patients receiving simultaneous resection, which could facilitate the clinical decision-making and inform future interventions for CRLM patients.
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Affiliation(s)
- Qichen Chen
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
| | - Jinghua Chen
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yiqiao Deng
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianjun Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianguo Zhou
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Baocai Xing
- Key Laboratory of Carcinogenesis and Translational Research, Hepatopancreatobiliary Surgery Department I, School of Oncology, Beijing Cancer Hospital and Institute, Peking University, Ministry of Education, Beijing, China.
| | - Yuan Li
- Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
| | - Kan Li
- Merck & Co., Inc., Rahway, NJ, USA.
| | - Hong Zhao
- Department of Hepatobiliary 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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Zheng Z, Chen H, Cai H, Zhu H. First-Line Tislelizumab for Advanced or Metastatic Esophageal Squamous Cell Carcinoma:A Cost-Effectiveness Analysis. Expert Rev Pharmacoecon Outcomes Res 2024; 24:397-404. [PMID: 38031985 DOI: 10.1080/14737167.2023.2290609] [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: 08/17/2023] [Accepted: 11/27/2023] [Indexed: 12/01/2023]
Abstract
OBJECTIVE The primary objective of this current study is to evaluate the cost-effectiveness of incorporating tislelizumab into the first-line treatment of metastatic or advanced esophageal squamous cell carcinoma (ESCC) in comparison to placebo with chemotherapy. METHOD We conducted a partitioned survival model with a time horizon of 10 years from a Chinese perspective. The direct medical costs were collected from the local setting in China. To enhance the credibility and robustness of the findings, sensitivity analyses were also conducted. RESULTS The inclusion of tislelizumab in conjunction with chemotherapy was shown to significantly enhance quality-adjusted life years (QALY) by 0.328 when compared to chemotherapy alone. This improvement comes at an additional cost of $9833.694. The incorporation of tislelizumab into the treatment regimen for advanced ESCC results in an incremental cost-effectiveness ratio (ICER) of $29980.774/QALY gained, which falls below the WTP threshold of $37304.346/QALY in China. One-way sensitivity analyses showed that no parameters were found to be adjustable within a specific range without altering the overall outcomes of our study. CONCLUSION Tislelizumab plus chemotherapy as first-line treatment for advanced or metastatic ESCC is may be a cost-effective option compared to chemotherapy alone.
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Affiliation(s)
- Zhiwei Zheng
- Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Hongcai Chen
- Department of Oncology Medicine, Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Hongfu Cai
- Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China
| | - Huide Zhu
- Department of Pharmacy, Cancer Hospital of Shantou University Medical College, Shantou, China
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Li Y, He Z, Wei J, Xu R, Liu T, Zhong Z, Liu L, Liang S, Zheng Y, Chen G, Lv Z, Huang S, Chen X, Sun H, Liu Y. Long-term exposure to ambient fine particulate matter constituents and mortality from total and site-specific gastrointestinal cancer. ENVIRONMENTAL RESEARCH 2024; 244:117927. [PMID: 38103778 DOI: 10.1016/j.envres.2023.117927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 11/22/2023] [Accepted: 12/10/2023] [Indexed: 12/19/2023]
Abstract
BACKGROUND Ambient fine particulate matter (PM2.5) exposure has been associated with an increased risk of gastrointestinal cancer mortality, but the attributable constituents remain unclear. OBJECTIVES To investigate the association of long-term exposure to PM2.5 constituents with total and site-specific gastrointestinal cancer mortality using a difference-in-differences approach in Jiangsu province, China during 2015-2020. METHODS We split Jiangsu into 53 spatial units and computed their yearly death number of total gastrointestinal, esophagus, stomach, colorectum, liver, and pancreas cancer. Utilizing a high-quality grid dataset on PM2.5 constituents, we estimated 10-year population-weighted exposure to black carbon (BC), organic carbon (OC), sulfate, nitrate, ammonium, and chloride in each spatial unit. The effect of constituents on gastrointestinal cancer mortality was assessed by controlling time trends, spatial differences, gross domestic product (GDP), and seasonal temperatures. RESULTS Overall, 524,019 gastrointestinal cancer deaths were ascertained in 84.77 million population. Each interquartile range increment of BC (0.46 μg/m3), OC (4.56 μg/m3), and nitrate (1.41 μg/m3) was significantly associated with a 27%, 26%, and 34% increased risk of total gastrointestinal cancer mortality, respectively, and these associations remained significant in PM2.5-adjusted models and constituent-residual models. We also identified robust associations of BC, OC, and nitrate exposures with site-specific gastrointestinal cancer mortality. The mortality risk generally displayed increased trends across the total exposure range and rose steeper at higher levels. We did not identify robust associations for sulfate, ammonium, or chlorine exposure. Higher mortality risk ascribed to constituent exposures was identified in total gastrointestinal and liver cancer among women, stomach cancer among men, and total gastrointestinal and stomach cancer among low-GDP regions. CONCLUSIONS This study offers consistent evidence that long-term exposure to PM2.5-bound BC, OC, and nitrate is associated with total and site-specific gastrointestinal cancer mortality, indicating that these constituents need to be controlled to mitigate the adverse effect of PM2.5 on gastrointestinal cancer mortality.
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Affiliation(s)
- Yingxin Li
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhimin He
- Department of Environmental Health, Nantong Center for Disease Control and Prevention, Nantong, Jiangsu, China
| | - Jing Wei
- Department of Atmospheric and Oceanic Science, Earth System Science Interdisciplinary Center, University of Maryland, College Park, MD, USA
| | - Ruijun Xu
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Tingting Liu
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zihua Zhong
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Likun Liu
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Sihan Liang
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yi Zheng
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Gongbo Chen
- Climate, Air Quality Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Ziquan Lv
- Central Laboratory of Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China
| | - Suli Huang
- Department of Environment and Health, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China
| | - Xi Chen
- National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Hong Sun
- Institute of Environment and Health, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China.
| | - Yuewei Liu
- Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China.
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Liu G, Li CM, Xie F, Li QL, Liao LY, Jiang WJ, Li XP, Lu GM. Colorectal cancer's burden attributable to a diet high in processed meat in the Belt and Road Initiative countries. World J Gastrointest Oncol 2024; 16:182-196. [PMID: 38292848 PMCID: PMC10824120 DOI: 10.4251/wjgo.v16.i1.182] [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: 10/01/2023] [Revised: 10/20/2023] [Accepted: 12/11/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) plays a significant role in morbidity, mortality, and economic cost in the Belt and Road Initiative ("B and R") countries. In addition, these countries have a substantial consumption of processed meat. However, the burden and trend of CRC in relation to the consumption of a diet high in processed meat (DHPM-CRC) in these "B and R" countries remain unknown. AIM To analyze the burden and trend of DHPM-CRC in the "B and R" countries from 1990 to 2019. METHODS We used the 2019 Global Burden of Disease Study to collate information regarding the burden of DHPM-CRC. Numbers and age-standardized rates (ASRs) of deaths along with the disability-adjusted life years (DALYs) were determined among the "B and R" countries in 1990 and 2019. Using joinpoint regression analysis, the average annual percent change (AAPC) was used to analyze the temporal trends of age-standardized DALYs rate (ASDALR) from 1990 to 2019 and in the final decade (2010-2019). RESULTS We found geographical differences in the burden of DHPM-CRC among "B and R" countries, with the three highest-ranking countries being the Russian Federation, China, and Ukraine in 1990, and China, the Russian Federation, and Poland in 2019. The burden of DHPM-CRC generally increased in most member countries from 1990 to 2019 (all P < 0.05). The absolute number of deaths and DALYs in DHPM-CRC were 3151.15 [95% uncertainty interval (UI) 665.74-5696.64] and 83249.31 (95%UI 15628.64-151956.31) in China in 2019. However, the number of deaths (2627.57-2528.51) and DALYs (65867.39-55378.65) for DHPM-CRC in the Russian Federation has declined. The fastest increase in ASDALR for DHPM-CRC was observed in Vietnam, Southeast Asia, with an AAPC value of 3.90% [95% confidence interval (CI): 3.63%-4.16%], whereas the fastest decline was observed in Kyrgyzstan, Central Asia, with an AAPC value of -2.05% (95% CI: -2.37% to -1.73%). A substantial upward trend in ASR of mortality, years lived with disability, years of life lost, and DALYs from DHPM-CRC changes in 1990-2019 and the final decade (2010-2019) for most Maritime Silk Route members in East Asia, South Asia, Southeast Asia, North Africa, and the Middle East, as well as Central Europe, while those of the most Land Silk Route members in Central Asia and Eastern Europe have decreased markedly (all P < 0.05). The ASDALR for DHPM-CRC increased more in males than in females (all P < 0.05). For those aged 50-74 years, the ASDALR for DHPM-CRC in 40 members exhibited an increasing trend, except for 20 members, including 7 members in Central Asia, Maldives, and 12 high or high-middle social development index (SDI) members in other regions (all P < 0.05). CONCLUSION The burden of DHPM-CRC varies substantially across "B and R" countries and threatens public health. Relevant evidence-based policies and interventions tailored to the different trends of countries in SDIs or Silk Routes should be adopted to reduce the future burden of CRC in "B and R" countries via extensive collaboration.
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Affiliation(s)
- Gu Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong Province, China
- Department of Gastrointestinal Surgery, Chenzhou Third People’s Hospital, Chenzhou 423000, Hunan Province, China
| | - Chang-Min Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong Province, China
- Department of Gastrointestinal Surgery, Chenzhou First People’s Hospital and the First Affiliated Hospital of Xiangnan University, Chenzhou, 423000 Hunan Province, China
| | - Fei Xie
- Department of Gastrointestinal Surgery, Chenzhou Third People’s Hospital, Chenzhou 423000, Hunan Province, China
| | - Qi-Lai Li
- Department of Gastrointestinal Surgery, Chenzhou Third People’s Hospital, Chenzhou 423000, Hunan Province, China
| | - Liang-Yan Liao
- Department of Breast and Thyroid Surgery, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Wen-Jun Jiang
- Department of Breast and Thyroid Surgery, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Xiao-Pan Li
- Department of Health Management Center, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai 200032, China
| | - Guan-Ming Lu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong Province, China
- Department of Breast and Thyroid Surgery, the Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
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Han Z, Wang N, Qiao Q, He X, Wang N. Association of PD-L1 Expression with Clinicopathologic Characters in Gastric Cancer: A Comprehensive Meta-analysis. Curr Med Chem 2024; 31:3198-3216. [PMID: 37921182 DOI: 10.2174/0109298673263784230922060257] [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: 05/24/2023] [Revised: 07/18/2023] [Accepted: 08/16/2023] [Indexed: 11/04/2023]
Abstract
PURPOSE The expression level of programmed death ligand-1(PD-L1) in patients with gastric cancer is the key to determining the use of immune drugs. The relationship between PD-L1 expression level and clinical characteristics is worth exploring. METHODS By setting the search terms correlated to PD-L1 and gastric cancer, a nearly comprehensive search was carried out in four major databases, and the deadline for searching was September 1, 2022. The retrieved documents were further screened by strict inclusion and exclusion criteria after removing the duplication. Next, the quality of the included studies was evaluated with the Newcastle-Ottawa Scale (NOS) scale. Finally, the STATA15.1 software was used to process data and draw plots, and the odds ratios (ORs) were adopted to assess the pooled effect size. RESULTS A total of 85 works of literature were included in this study through screening strictly, and detailed data were extracted after evaluating the quality of the literature. The process of analysis was conducted in the whole population, Asia-Africa population, European and American population, and Asian population with CPS≥1, amd all found that the expression of PD-L1 in gastric cancer was correlated with age, tumor size, EBV infection, Her-2 expression and microsatellite status. However, the subgroup of the region also found some differences in Asian and Western regions, which was interesting and worth studying further. The included research of this study did not have significant publish bias. CONCLUSION After careful analysis, this study found that age (>60 years), tumor size (>5cm), EBV infection (+), Her-2 expression (+), microsatellite status (MSI), and mismatch repair status (dMMR) were risk factors for positive expression of PD-L1 in gastric cancer.
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Affiliation(s)
- Zhuo Han
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Nan Wang
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Qing Qiao
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Xianli He
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
| | - Nan Wang
- Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China
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