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Yuan XW, Feng JH, Huang DB, Lu ZT, Ye HL, Chen P, Deng L. The combination of CA125, CA199, CEA, and AFP is an effective diagnostic biomarker for gastric cancer in elderly individuals. World J Surg Oncol 2025; 23:142. [PMID: 40221735 PMCID: PMC11992887 DOI: 10.1186/s12957-025-03789-z] [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: 02/14/2025] [Accepted: 03/29/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND Serum tumour markers (TMs) such as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and CA125 have been established as prognostic indicators for gastric cancer (GC); however, the diagnostic value of these markers for GC in older adults has yet to be examined. Therefore, this study aimed to explore the diagnostic and prognostic significance of AFP, CEA, CA199 and CA125 for GC in elderly individuals. METHODS A total of 188 patients who visited The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, from May 2021 to March 2024 were selected for this study. TMs, namely, CA199, CA125, CEA, and AFP, were examined in all patients. Comparisons of these TMs were conducted among the three groups, and TM levels were compared in patients with GC at various TNM stages. The diagnostic value of these TMs for GC was evaluated by calculating the area under the curve (AUC). RESULTS We selected 89 patients diagnosed with GC: 52 patients with benign gastric diseases and 47 healthy individuals for our study. The positivity rates of AFP, CA125, CEA and CA199 were significantly greater in the GC group (31.46%, 31.46%, 43.82% and 23.60%, respectively) than in the benign gastric disease group and healthy control group. The diagnostic sensitivities of CEA, CA125, CA199 and AFP for GC were 31.46%, 29.21%, 44.90% and 24.72%, respectively. The combination of these markers yielded a sensitivity of 65.17%, which was significantly greater than the sensitivity of each marker alone (P < 0.05). Additionally, patients with stage I-II disease had significantly lower serum levels of CEA, CA199, CA125, and AFP than did those with stage III-IV disease. CONCLUSIONS The levels of serum TMs, including CA12-5, CEA, CA199 and AFP, are elevated in elderly individuals with GC, indicating a higher TNM stage. The combination of CEA, CA12-5, CA199 and AFP has enhanced diagnostic value for GC, thereby offering significant clinical guidance. However, this study is limited by its retrospective design and lack of external validation, which should be addressed in future prospective trials.
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Affiliation(s)
- Xiao-Wen Yuan
- Department of Laboratory Medicine of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528200, Guangdong, China.
- Department of Laboratory Medicine of People's Hospital of Rongjiang County, Rongjiang, 557200, Guizhou, China.
| | - Jia-Hao Feng
- Department of Laboratory Medicine of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528200, Guangdong, China
| | - De Bing Huang
- Department of Laboratory Medicine of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528200, Guangdong, China
| | - Zhan-Tao Lu
- Department of Laboratory Medicine of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528200, Guangdong, China
| | - Hui-Ling Ye
- Department of Laboratory Medicine of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528200, Guangdong, China
| | - Ping Chen
- Department of Laboratory Medicine of The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Foshan, 528200, Guangdong, China
| | - Lv Deng
- Department of Gastroenterology of Eighth People's Hospital of Nanhai District, Foshan City, 528216, Guangdong, China.
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Sun A, Chen H, Shi X, Shang Z, Zhang J. Diagnostic Value of Joint Detection of Serum TK1, TSGF, CA199, and CA724 for Gastric Cancer and Its Relationship With Clinicopathologic Features and Prognosis. Am Surg 2025; 91:570-578. [PMID: 39668434 DOI: 10.1177/00031348241307397] [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] [Indexed: 12/14/2024]
Abstract
ObjectiveTo assess the diagnostic value of joint detection of serum TK1, TSGF, CA199, and CA724 for gastric cancer and its relationship with clinicopathologic features and prognosis.MethodsThe 105 gastric cancer patients were enrolled. The diagnostic value of serum TK1, TSGF, CA199, and CA724 for gastric cancer and the relationship between these indicators and the clinicopathologic characteristics of gastric cancer patients were evaluated. During the follow-up period, recurrence, metastasis, and death were considered as poor prognosis. The relationships between serum TK1, TSGF, CA199, and CA724 levels and poor prognosis and factors affecting the poor prognosis of gastric cancer patients were analyzed.ResultsTK1, TSGF, CA199, and CA724 levels in the gastric cancer group were higher; serum TK1, TSGF, CA199, and CA724 levels were higher in gastric cancer patients with tumor diameters ≥3 cm, TNM stages III and IV, low/moderate degree of differentiation, infiltration depths of the muscular or plasma layer, and lymphatic metastases; AUC of combined TK1, TSGF, CA199, and CA724 (0.894) was higher than that of the four indicators alone; the percentage of gastric cancer patients with poor prognosis in patients with low serum TK1, TSGF, CA199, and CA724 levels was lower; serum TK1, TSGF, CA199, and CA724 levels were factors influencing poor prognosis of gastric cancer patients (all P < 0.05).ConclusionElevated serum levels of TK1, TSGF, CA199, and CA724 are associated with clinicopathologic features and poor prognosis of gastric cancer and may be used as serum biomarkers for prognostic evaluation of gastric cancer patients.
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Affiliation(s)
- Aiwen Sun
- Clinical Laboratory, The Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Hui Chen
- Department of Gastroenterology, The Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Xiaojuan Shi
- Department of Gastroenterology, The Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Zhanmin Shang
- Department of Gastroenterology, The Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Jishun Zhang
- Department of Gastroenterology, The Affiliated Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
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Feng X, Zhang J, Liu J, Su J, Liu X, Yang M, Peng Y, Yan H, Chen Z. A stable thymidine kinase 1 tetramer for improved quality control of serum level quantification. Clin Chim Acta 2025; 565:119967. [PMID: 39304108 DOI: 10.1016/j.cca.2024.119967] [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: 05/07/2024] [Revised: 07/30/2024] [Accepted: 09/11/2024] [Indexed: 09/22/2024]
Abstract
DNA synthesis is a critical process for cell growth and division. In cancer patients, an enzyme called thymidine kinase 1 (TK1) is often elevated in the blood, making it a valuable biomarker for cancer diagnosis and treatment. However, previous studies have shown that recombinant TK1 can exist in unstable mixtures of tetramers and dimers, leading to inconsistent results and potentially affecting accuracy. To address this issue, we hypothesized that incorporating tetrameric coiled-coil peptides could enhance TK1 self-assembly into stable tetramers without requiring additional adenosine triphosphate. In this study, we successfully expressed a recombinant TK1 tetramer protein in the Escherichia coli system. We optimized the induction conditions, significantly increasing protein expression levels, functionality, and solubility. Size exclusion chromatography confirmed the formation of a tetrameric structure in the expressed TK1 protein, with a molecular weight of 127.2 KDa, consistent with our expectations. We also found that the TK1 tetramer exhibited higher affinity with anti-TK1 IgY than wild-type TK1, as shown by enzyme-linked immunosorbent assay experiments. Moreover, the TK1 tetramer demonstrated good stability against heating, freeze-thawing and lyophilization with almost no immunoactivity lost. These findings suggest that recombinant TK1 tetramers have the potential to serve as calibrators in diagnostic assay kits, becoming promising candidates for quality control of clinical laboratory and in vitro diagnostic reagents.
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Affiliation(s)
- Xiangning Feng
- NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, 1 Sun Yat-Sen University, Guangzhou 510080, China; One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China
| | - Jinsong Zhang
- NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, 1 Sun Yat-Sen University, Guangzhou 510080, China; One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China
| | - Jinsong Liu
- NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, 1 Sun Yat-Sen University, Guangzhou 510080, China; One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China
| | - Jiayue Su
- NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, 1 Sun Yat-Sen University, Guangzhou 510080, China; One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China
| | - Xinrui Liu
- NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, 1 Sun Yat-Sen University, Guangzhou 510080, China; One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China
| | - Mingwei Yang
- NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, 1 Sun Yat-Sen University, Guangzhou 510080, China; One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China
| | - Yuanli Peng
- NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, 1 Sun Yat-Sen University, Guangzhou 510080, China; One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China
| | - Haozhen Yan
- NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, 1 Sun Yat-Sen University, Guangzhou 510080, China; One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China
| | - Zeliang Chen
- NMPA Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products, 1 Sun Yat-Sen University, Guangzhou 510080, China; One Health Center of Excellence for Research and Training, School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China; Key Laboratory of Tropical Diseases Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China; Key Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Medical College, Inner Mongolia Minzu University, Tongliao 028000, China; Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Shenyang Agricultural University, Shenyang 110866, China.
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Li W, Zhong Q, Deng N, Wang H, Ouyang J, Guan Z, Zhou X, Li K, Sun X, Wang Y. Identification of a novel prognostic model for gastric cancer utilizing glutamine-related genes. Heliyon 2024; 10:e37985. [PMID: 39386842 PMCID: PMC11462029 DOI: 10.1016/j.heliyon.2024.e37985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 08/23/2024] [Accepted: 09/16/2024] [Indexed: 10/12/2024] Open
Abstract
BACKGROUND Glutamine metabolism presents a promising avenue for cancer prevention and treatment, but the underlying mechanisms in gastric cancer (GC) progression remain elusive. METHODS The TCGA-STAD and GEO GSE62254 datasets, containing gene expression, clinical information, and survival outcomes of GC, were meticulously examined. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to excavate a key module (MEturquoise), which was used to intersect with glutamine metabolism-related genes (GMRGs) and differentially expressed genes (DEGs) to identify differentially expressed GMRGs (DE-GMRGs). LASSO and Cox Univariate analyses were implemented to determine risk model genes. Correlation of the risk model with clinical parameters, pathways, and tumor immune microenvironments, was analyzed, and its prognostic independence was validated by Cox analyses. Finally, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to validate the expression levels of MYB, LRFN4, LMNB2, and SLC1A5 in GC and para-carcinoma tissue. RESULTS The excavation of 4521 DEGs led to the discovery of the key MEturquoise module, which exhibited robust correlations with GC traits. The intersection analysis identified 42 DE-GMRGs, among which six genes showed consistency. Further LASSO analysis established MYB, LRFN4, LMNB2, and SLC1A5 as pivotal risk model genes. The risk model demonstrated associations with oncogenic and metabolism-related pathways, inversely correlating with responses to immune checkpoint blockade therapies. This risk model, together with "age", was validated to be an independent prognostic factor for GC. RT-qPCR result indicated that MYB, LRFN4, LMNB2, and SLC1A5 expressions were remarkably up-regulated in GC tissues comparison with para-carcinoma tissue. CONCLUSION The present study has generated a novel risk module containing four DE-GMRGs for predicting the prognosis and the response to immune checkpoint blockade treatments for GC. This risk model provides new insights into the involvement of glutamine metabolism in GC, warranting further investigation.
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Affiliation(s)
- Weidong Li
- Department of Gastrointestinal Surgery, Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China
| | - Qixing Zhong
- Department of Gastrointestinal Surgery, Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China
| | - Naisheng Deng
- Department of Gastrointestinal Surgery, Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China
| | - Haitao Wang
- Department of Gastrointestinal Surgery, Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China
| | - Jun Ouyang
- Department of Gastrointestinal Surgery, Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China
| | - Zhifen Guan
- Department of Gastrointestinal Surgery, Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China
| | - Xinhao Zhou
- Department of Gastrointestinal Surgery, Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China
| | - Kai Li
- Department of Gastrointestinal Surgery, Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China
| | - Xueying Sun
- Department of Molecular Medicine & Pathology, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, 1142, New Zealand
| | - Yao Wang
- Department of Gastrointestinal Surgery, Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China
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Shi Y, Qiu A, Cui H, Lv H, Zhou L. Identification of an autophagy- and macropinocytosis-related prognostic signature for the prediction of prognosis and therapeutic response in gastric cancer. Genes Genomics 2024; 46:1149-1164. [PMID: 39150612 DOI: 10.1007/s13258-024-01557-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 08/08/2024] [Indexed: 08/17/2024]
Abstract
BACKGROUND Traditional liquid biopsy markers show a low rate of positivity and accurate in gastric cancer. With the rapid advancement of sequencing technology, scientists have identified promising research avenues in this field. Autophagy and macropinocytosis utilize diverse pathways and mechanisms to supply resources and fuel for tumor growth. Nonetheless, their potential interplay introduces an untapped avenue for the discovery of novel tumor biomarkers. OBJECTIVE To develop an innovative prognostic signature based on autophagy- and micropinocytosis-related genes, with the aim to predict the outcome and therapeutic response of gastric cancer patients. Additionally, to validate the prognostic impact of this signature, and elucidate the role of representative molecules in gastric cancer. METHODS To construct and validate a prognostic signature for gastric cancer, bioinformatics methods such as COX regression, LASSO regression, survival analysis, ROC curve, and nomogram were utilized based on the sequencing and clinical data of gastric cancer patients retrieved from the TCGA and GEO databases. GSEA functional enrichment analyses were employed to predict the biological functions. Meanwhile, qRT-PCR and Western blot experiments were utilized to quantify the mRNA and protein expression levels. Furthermore, the EdU assay and colony formation assay were utilized to examine the cell proliferation ability while the Transwell assays were conducted to assess the migration and invasion abilities of gastric cancer cells. RESULTS Through consistency clustering and univariate COX analyses, potential prognostic genes involved in both autophagy and macropinocytosis were identified. Based on these genes, a 9-gene signature was constructed, which demonstrated high accuracy in predicting gastric cancer patients' survival period, immunotherapeutic response, and chemotherapy drug tolerance. Furthermore, qRT-PCR analyses of gastric cancer tissue samples showed that the representative genes of this signature were aberrantly overexpressed in gastric cancer, with MATN3, as the most notable molecule, exhibiting significant carcinogenic effects on cancer cells by actively regulating their proliferation, migration, and invasion abilities. CONCLUSION Our newly created prognostic signature possesses significant potential as a biomarker for gastric cancer, while MATN3 is identified as an oncogenic factor in gastric cancer. This brings to light new perspectives, which can contribute to enhancing the diagnosis and treatment of gastric cancer.
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Affiliation(s)
- Yuhua Shi
- Department of General Surgery, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, No. 75, Juchang Road, Yancheng, 224001, China
- Central Laboratory of Yancheng Third People's Hospital, Yancheng, China
| | - Aifeng Qiu
- Department of General Surgery, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, No. 75, Juchang Road, Yancheng, 224001, China
- Central Laboratory of Yancheng Third People's Hospital, Yancheng, China
| | - Hengfeng Cui
- Department of General Surgery, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, No. 75, Juchang Road, Yancheng, 224001, China
- Central Laboratory of Yancheng Third People's Hospital, Yancheng, China
| | - Heng Lv
- The First Clinical School, Xuzhou Medical University, No. 99, Huaihai West Road, Xuzhou, 221002, China.
| | - Lei Zhou
- Department of General Surgery, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital, No. 75, Juchang Road, Yancheng, 224001, China.
- Central Laboratory of Yancheng Third People's Hospital, Yancheng, China.
- The Graduate School, Dalian Medical University, Dalian, China.
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Nakane K, Yagi K, Yajima S, Nomura S, Sugimoto M, Seto Y. Salivary metabolomic biomarkers for esophageal and gastric cancers by liquid chromatography-mass spectrometry. Cancer Sci 2024; 115:3089-3098. [PMID: 39004809 PMCID: PMC11463073 DOI: 10.1111/cas.16256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 05/24/2024] [Accepted: 06/12/2024] [Indexed: 07/16/2024] Open
Abstract
Early detection of esophageal and gastric cancers is essential for patients' prognosis; however, optimal noninvasive screening tests are currently not available. Saliva is a biofluid that is readily available, allowing for frequent screening tests. Thus, we explored salivary diagnostic biomarkers for esophageal and gastric cancers using metabolomic analyses. Saliva samples were collected from patients with esophageal (n = 50) and gastric cancer (n = 63), and patients without cancer as controls (n = 20). Salivary metabolites were analyzed by liquid chromatography-mass spectrometry to identify salivary biomarkers. We also examined the metabolic profiles of gastric cancer tissues and compared them with the salivary biomarkers. The sensitivity of the diagnostic models based on salivary biomarkers was assessed by comparing it with that of serum tumor markers. Additionally, using postoperative saliva samples collected from patients with gastric cancer, we analyzed the changes in the biomarkers' concentrations before and after surgery. Cytosine was detected as a salivary biomarker for gastric cancer, and cytosine, 2-oxoglutarate, and arginine were detected as salivary biomarkers for esophageal cancer. Cytidine, a cytosine nucleotide, showed decreased concentrations in gastric cancer tissues. The sensitivity of the diagnostic models for esophageal and gastric cancers was 66.0% and 47.6%, respectively, while that of serum tumor markers was 40%. Salivary cytosine concentration increased significantly postoperatively relative to the preoperative value. In summary, we identified salivary biomarkers for esophageal and gastric cancers, which showed diagnostic sensitivity at least comparable to that of serum tumor markers. Salivary metabolomic tests could be promising screening tests for these types of cancer.
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Affiliation(s)
- Kosuke Nakane
- Department of Gastrointestinal Surgery, Graduate School of MedicineUniversity of TokyoTokyoJapan
| | - Koichi Yagi
- Department of Gastrointestinal Surgery, Graduate School of MedicineUniversity of TokyoTokyoJapan
| | - Sho Yajima
- Department of Gastrointestinal Surgery, Graduate School of MedicineUniversity of TokyoTokyoJapan
| | - Sachiyo Nomura
- Department of Gastrointestinal Surgery, Graduate School of MedicineUniversity of TokyoTokyoJapan
| | - Masahiro Sugimoto
- Institute of Medical ScienceTokyo Medical UniversityTokyoJapan
- Institute for Advanced BiosciencesKeio UniversityTsuruokaJapan
| | - Yasuyuki Seto
- Department of Gastrointestinal Surgery, Graduate School of MedicineUniversity of TokyoTokyoJapan
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Sun AH, Zhang XY, Huang YY, Chen L, Wang Q, Jiang XC. Prognostic value and predictive model of tumor markers in stage I to III gastric cancer patients. World J Clin Oncol 2024; 15:1033-1047. [PMID: 39193154 PMCID: PMC11346068 DOI: 10.5306/wjco.v15.i8.1033] [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: 03/20/2024] [Revised: 07/03/2024] [Accepted: 07/24/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Preoperative serum tumor markers have been widely used in the diagnosis and treatment of gastric cancer patients. However, few studies have evaluated the prognosis of gastric cancer patients by establishing statistical models with multiple serum tumor indicators. AIM To explore the prognostic value and predictive model of tumor markers in stage I and III gastric cancer patients. METHODS From October 2018 to April 2020, a total of 1236 patients with stage I to III gastric cancer after surgery were included in our study. The relationship between serum tumor markers and clinical and pathological data were analyzed. We established a statistical model to predict the prognosis of gastric cancer based on the results of COX regression analysis. Overall survival (OS) was also compared across different stages of gastric cancer. RESULTS The deadline for follow-up was May 31, 2023. A total of 1236 patients were included in our study. Univariate analysis found that age, clinical stage, T and N stage, tumor location, differentiation, Borrmann type, size, and four serum tumor markers were prognostic factors of OS (P < 0.05). It was shown that clinical stage, tumor size, alpha foetoprotein, carcinoembryonic antigen, CA125 and CA19-9 (P < 0.05) were independent prognostic factors for OS. According to the scoring results obtained from the statistical model, we found that patients with high scores had poorer survival time (P < 0.05). Furthermore, in stage I patients, the 3-year OS for scores 0-3 ranged from 96.85%, 95%, 85%, and 80%. In stage II patients, the 3-year OS for scores 0-4 were 88.6%, 76.5%, 90.5%, 65.5% and 60%. For stage III patients, 3-year OS for scores 0-6 were 70.9%, 68.3%, 64.1%, 50.9%, 38.4%, 18.5% and 5.2%. We also analyzed the mean survival of patients with different scores. For stage I patients, the mean OS was 55.980 months. In stage II, the mean OS was 51.550 months. The mean OS for stage III was 39.422 months. CONCLUSION Our statistical model can effectively predict the prognosis of gastric cancer patients.
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Affiliation(s)
- Ai-Hua Sun
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
| | - Xin-Yu Zhang
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
| | - Yang-Yang Huang
- Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou 350001, China
| | - Lei Chen
- Department of General Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China
| | - Qing Wang
- Department of General Surgery, Xiang'an Hospital of Xiamen University, Xiamen 361102, Fujian Province, China
| | - Xiao-Cong Jiang
- Department of Radiotherapy Oncology, Huizhou Municipal Central Hospital, Huizhou 516001, Guangdong Province, China
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Zhou CM, Zhao SH. Evaluation of the value of combined detection of tumor markers CA724, carcinoembryonic antigen, CA242, and CA19-9 in gastric cancer. World J Gastrointest Oncol 2024; 16:1737-1744. [PMID: 38764828 PMCID: PMC11099441 DOI: 10.4251/wjgo.v16.i5.1737] [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: 01/12/2024] [Revised: 02/08/2024] [Accepted: 03/20/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND Gastric cancer is a global health concern that poses a significant threat to human well-being. AIM To detecting serum changes in carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 724, CA242, and CA19-9 expression among patients with gastric cancer. METHODS Eighty patients diagnosed with gastric cancer between January 2020 and January 2023 were included in the observation group, while 80 patients with benign gastric diseases were included in the control group. Both groups were tested for tumor markers (CA724, CEA, CA242, and CA19-9]. Tumor marker indicators (CA724, CEA, CA242, and CA19-9) were compared between the two groups, assessing positive rates of tumor markers across various stages in the observation group. Additionally, single and combined detection of various tumor markers were examined. RESULTS The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value observed for the combined detection of CA724, CEA, CA242, and CA19-9 were higher than those of CA724, CEA, CA242, and CA19-9 individually. Therefore, the combined detection of CA724, CEA, CA242, and CA19-9 has a high diagnostic accuracy and could reduce the occurrence of missed or misdiagnosed cases, facilitating the early diagnosis and treatment of patients. CONCLUSION CA724, CEA, CA242, and CA19-9 serum levels in gastric cancer patients significantly surpassed those in non-gastric cancer patients (P < 0.05). Their combined detection can improve the diagnostic accuracy for gastric cancer, warranting clinical promotion.
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Affiliation(s)
- Chong-Mei Zhou
- Department of Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou 450003, Henan Province, China
| | - Shao-Hua Zhao
- Department of Clinical Laboratory, Henan Provincial People's Hospital, Zhengzhou 450003, Henan Province, China
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Liu B, Xu YJ, Chu FR, Sun G, Zhao GD, Wang SZ. Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer. World J Gastrointest Surg 2024; 16:396-408. [PMID: 38463346 PMCID: PMC10921200 DOI: 10.4240/wjgs.v16.i2.396] [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: 08/25/2023] [Revised: 11/05/2023] [Accepted: 01/19/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND The efficacy of neoadjuvant chemotherapy (NAC) in advanced gastric cancer (GC) is still a controversial issue. AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC. METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020. Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors. A nomogram model was employed to predict the response to NAC. RESULTS In total 230 patients were finally included in this study, including 154 males (67.0%) and 76 females (33.0%). The mean age was (59.37 ± 10.60) years, ranging from 24 years to 80 years. According to the tumor regression grade standard, there were 95 cases in the obvious response group (grade 0 or grade 1) and 135 cases in the poor response group (grade 2 or grade 3). The obvious response rate was 41.3%. Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location (P < 0.001), histological differentiation (P = 0.001), clinical T stage (P = 0.008), and carbohydrate antigen 724 (P = 0.008). The C-index for the prediction nomogram was 0.806. The calibration curve revealed that the predicted value exhibited good agreement with the actual value. Decision curve analysis showed that the nomogram had a good value in clinical application. CONCLUSION A nomogram combining tumor location, histological differentiation, clinical T stage, and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.
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Affiliation(s)
- Bing Liu
- Department of Gastrointestinal Surgery, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou 570208, Hainan Province, China
| | - Yu-Jie Xu
- Department of Gastrointestinal Surgery, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou 570208, Hainan Province, China
| | - Feng-Ran Chu
- Clinical College, Hainan Medical University, Haikou 571199, Hainan Province, China
| | - Guang Sun
- Department of Gastrointestinal Surgery, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou 570208, Hainan Province, China
| | - Guo-Dong Zhao
- Department of Gastrointestinal Surgery, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou 570208, Hainan Province, China
| | - Sheng-Zhong Wang
- Department of Gastrointestinal Surgery, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou 570208, Hainan Province, China
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10
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Bitter EE, Skidmore J, Allen CI, Erickson RI, Morris RM, Mortimer T, Meade A, Brog R, Phares T, Townsend M, Pickett BE, O’Neill KL. TK1 expression influences pathogenicity by cell cycle progression, cellular migration, and cellular survival in HCC 1806 breast cancer cells. PLoS One 2023; 18:e0293128. [PMID: 38033034 PMCID: PMC10688958 DOI: 10.1371/journal.pone.0293128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 10/05/2023] [Indexed: 12/02/2023] Open
Abstract
Breast cancer is the most common cancer diagnosis worldwide accounting for 1 out of every 8 cancer diagnoses. The elevated expression of Thymidine Kinase 1 (TK1) is associated with more aggressive tumor grades, including breast cancer. Recent studies indicate that TK1 may be involved in cancer pathogenesis; however, its direct involvement in breast cancer has not been identified. Here, we evaluate potential pathogenic effects of elevated TK1 expression by comparing HCC 1806 to HCC 1806 TK1-knockdown cancer cells (L133). Transcriptomic profiles of HCC 1806 and L133 cells showed cell cycle progression, apoptosis, and invasion as potential pathogenic pathways affected by TK1 expression. Subsequent in-vitro studies confirmed differences between HCC 1806 and L133 cells in cell cycle phase progression, cell survival, and cell migration. Expression comparison of several factors involved in these pathogenic pathways between HCC 1806 and L133 cells identified p21 and AKT3 transcripts were significantly affected by TK1 expression. Creation of a protein-protein interaction map of TK1 and the pathogenic factors we evaluated predict that the majority of factors evaluated either directly or indirectly interact with TK1. Our findings argue that TK1 elevation directly increases HCC 1806 cell pathogenicity and is likely occurring by p21- and AKT3-mediated mechanisms to promote cell cycle arrest, cellular migration, and cellular survival.
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Affiliation(s)
- Eliza E. Bitter
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Jonathan Skidmore
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Carolyn I. Allen
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Rachel I. Erickson
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Rachel M. Morris
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Toni Mortimer
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Audrey Meade
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Rachel Brog
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Tim Phares
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Michelle Townsend
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
- Thunder Biotech Inc., Provo, Utah, United States of America
| | - Brett E. Pickett
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
| | - Kim L. O’Neill
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah, United States of America
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11
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Repetto O, Vettori R, Steffan A, Cannizzaro R, De Re V. Circulating Proteins as Diagnostic Markers in Gastric Cancer. Int J Mol Sci 2023; 24:16931. [PMID: 38069253 PMCID: PMC10706891 DOI: 10.3390/ijms242316931] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/22/2023] [Accepted: 11/24/2023] [Indexed: 12/18/2023] Open
Abstract
Gastric cancer (GC) is a highly malignant disease affecting humans worldwide and has a poor prognosis. Most GC cases are detected at advanced stages due to the cancer lacking early detectable symptoms. Therefore, there is great interest in improving early diagnosis by implementing targeted prevention strategies. Markers are necessary for early detection and to guide clinicians to the best personalized treatment. The current semi-invasive endoscopic methods to detect GC are invasive, costly, and time-consuming. Recent advances in proteomics technologies have enabled the screening of many samples and the detection of novel biomarkers and disease-related signature signaling networks. These biomarkers include circulating proteins from different fluids (e.g., plasma, serum, urine, and saliva) and extracellular vesicles. We review relevant published studies on circulating protein biomarkers in GC and detail their application as potential biomarkers for GC diagnosis. Identifying highly sensitive and highly specific diagnostic markers for GC may improve patient survival rates and contribute to advancing precision/personalized medicine.
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Affiliation(s)
- Ombretta Repetto
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy
| | - Roberto Vettori
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy; (R.V.); (A.S.)
| | - Agostino Steffan
- Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy; (R.V.); (A.S.)
| | - Renato Cannizzaro
- Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy;
- Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy
| | - Valli De Re
- Facility of Bio-Proteomics, Immunopathology and Cancer Biomarkers, Centro di Riferimento Oncologico di Aviano (CRO), National Cancer Institute, IRCCS, 33081 Aviano, Italy
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12
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Sun C, Niu P, Zhang X, Zhao L, Wang W, Luan X, Han X, Chen Y, Zhao D. Concurrent clinical and pathological response predicts favorable prognosis of patients with gastric cancer after neoadjuvant therapy: a real-world study. BMC Cancer 2023; 23:996. [PMID: 37853387 PMCID: PMC10585908 DOI: 10.1186/s12885-023-11508-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 10/10/2023] [Indexed: 10/20/2023] Open
Abstract
BACKGROUND Response of locally advanced gastric cancer (LAGC) to neoadjuvant therapy (NAT) may be associated with prognosis, but which of the clinical or pathological evaluation can accurately predict a favorable prognosis is still controversial. This study aims to compare the effect of clinical and pathological response on the prognosis of patients with gastric cancer. METHODS This study retrospectively analyzed LAGC patients who underwent NAT followed by surgery in the China National Cancer Center from January 2004 to January 2021. Clinical and pathological responses after NAT were evaluated using RECIST 1.1 and Mandard tumor regression grade system (TRG) respectively. Complete response (CR) and partial response (PR) assessed by computed tomography were regarded as clinical response. For histopathology regression assessment, response was defined as Mandard 1, 2, 3 and non-response as Mandard 4, 5. Furthermore, we combined clinical and pathological evaluation results into a variable termed "comprehensive assessment" and divided it into four groups based on the presence or absence of response (concurrent response, only clinical response, only pathological response, both non-response). The association between the prognosis and clinicopathological factors was assessed in univariate and multivariate Cox regression analysis. RESULTS In total, 238 of 1073 patients were included in the study after screening. The postoperative pathological response rate and clinical response rate were 50.84% (121/238) and 39.92% (95/238), respectively. 154 patients got consistent results in clinical and pathological evaluation (66 were concurrent response and 88 were both non-response), while the other 84 patients did not. The kappa value was 0.297(p < 0.001), which showed poor consistency. Multivariate Cox regression analysis revealed that comprehensive assessment (P = 0.03), clinical N stage(P < 0.001), vascular or lymphatic invasion (VOLI) (HR 2.745, P < 0.001), and pre-CA724(HR 1.577, P = 0.047) were independent factors for overall survival in patients with gastric cancer. Among four groups in the comprehensive assessment, concurrent response had significantly better survival (median OS: 103.5 months) than the other groups (P = 0.008). CONCLUSION Concurrent clinical and pathological response might predict a favorable prognosis of patients with gastric cancer after neoadjuvant therapy, further validation is needed in prospective clinical trials with larger samples.
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Affiliation(s)
- Chongyuan Sun
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Penghui Niu
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaojie Zhang
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lulu Zhao
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wanqing Wang
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoyi Luan
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xue Han
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yingtai Chen
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Dongbing Zhao
- National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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13
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Li Y, Li J, Meng M, Duan S, Shi H, Hang J. Development and Validation of a Radiomics Nomogram for Liver Metastases Originating from Gastric and Colorectal Cancer. Diagnostics (Basel) 2023; 13:2937. [PMID: 37761304 PMCID: PMC10528017 DOI: 10.3390/diagnostics13182937] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/04/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
The origin of metastatic liver tumours (arising from gastric or colorectal sources) is closely linked to treatment choices and survival prospects. However, in some instances, the primary lesion remains elusive even after an exhaustive diagnostic investigation. Consequently, we have devised and validated a radiomics nomogram for ascertaining the primary origin of liver metastases stemming from gastric cancer (GCLMs) and colorectal cancer (CCLMs). This retrospective study encompassed patients diagnosed with either GCLMs or CCLMs, comprising a total of 277 GCLM cases and 278 CCLM cases. Radiomic characteristics were derived from venous phase computed tomography (CT) scans, and a radiomics signature (RS) was computed. Multivariable regression analysis demonstrated that gender (OR = 3.457; 95% CI: 2.102-5.684; p < 0.001), haemoglobin levels (OR = 0.976; 95% CI: 0.967-0.986; p < 0.001), carcinoembryonic antigen (CEA) levels (OR = 0.500; 95% CI: 0.307-0.814; p = 0.005), and RS (OR = 2.147; 95% CI: 1.127-4.091; p = 0.020) exhibited independent associations with GCLMs as compared to CCLMs. The nomogram, combining RS with clinical variables, demonstrated strong discriminatory power in both the training (AUC = 0.71) and validation (AUC = 0.78) cohorts. The calibration curve, decision curve analysis, and clinical impact curves revealed the clinical utility of this nomogram and substantiated its enhanced diagnostic performance.
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Affiliation(s)
- Yuying Li
- Department of Radiology, Changzhou Second People’s Hospital Affiliated with Nanjing Medical University, Changzhou 213000, China; (Y.L.); (J.L.); (M.M.)
- Graduate College, Dalian Medical University, Dalian 116000, China
| | - Jingjing Li
- Department of Radiology, Changzhou Second People’s Hospital Affiliated with Nanjing Medical University, Changzhou 213000, China; (Y.L.); (J.L.); (M.M.)
- Graduate College, Dalian Medical University, Dalian 116000, China
| | - Mingzhu Meng
- Department of Radiology, Changzhou Second People’s Hospital Affiliated with Nanjing Medical University, Changzhou 213000, China; (Y.L.); (J.L.); (M.M.)
| | - Shaofeng Duan
- GE Healthcare, Precision Health Institution, Shanghai 201100, China;
| | - Haifeng Shi
- Department of Radiology, Changzhou Second People’s Hospital Affiliated with Nanjing Medical University, Changzhou 213000, China; (Y.L.); (J.L.); (M.M.)
| | - Junjie Hang
- Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China
- Department of Oncology, Changzhou Second People’s Hospital Affiliated with Nanjing Medical University, Changzhou 213000, China
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14
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Huang P, Zhou X, Zheng M, Yu Y, Jin G, Zhang S. Regulatory T cells are associated with the tumor immune microenvironment and immunotherapy response in triple-negative breast cancer. Front Immunol 2023; 14:1263537. [PMID: 37767092 PMCID: PMC10521732 DOI: 10.3389/fimmu.2023.1263537] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 08/25/2023] [Indexed: 09/29/2023] Open
Abstract
Introduction Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a high risk of distant metastasis, an extremely poor prognosis, and a high risk of death. Regulatory T cells (Tregs) contribute to the formation of a tumor immunosuppressive microenvironment, which plays an important role in the progression and treatment resistance of TNBC. Methods A public single-cell sequencing dataset demonstrated increased infiltration of Tregs in TNBC tissues relative to normal breast tissue. Weighted gene co-expression network analysis was used to identify Treg infiltration-related modules for METABRIC TNBC samples. Subsequently, we obtained two Treg infiltration-associated clusters of TNBC by applying consensus clustering and further constructed a prognostic model based on this Treg infiltration-associated gene module. The ability of the selected gene in the prognostic model, thymidine kinase-1 (TK1), to promote the progression of TNBC was evaluated in vitro. Results We concluded that two Treg infiltration-associated clusters had different prognoses and sensitivities to drugs commonly used in breast cancer treatment, and multi-omics analysis revealed that the two clusters had different copy number variations of key tumor progression genes. The 7-gene risk score based on TNBC Treg infiltration was a reliable prognostic indicator both in the training and validation cohorts. Moreover, patients with TNBC with high Treg infiltration-related scores lacked the activation of immune activation pathways and exhibited resistance to anti-PD1 immunotherapy. Knocking down TK1 led to impaired proliferation, migration, and invasion of TNBC cells in vitro. In addition, specimens from patients with TNBC with high TK1 expression showed significantly higher Treg infiltration in tumors. Results of spatial transcriptome analysis showed that TK1 positive cells mainly localize in tumor area, and Treg cell infiltration in TNBC tissues was associated with high expression of TK1. Pan-cancer analysis also demonstrated that TK1 is associated with poor prognosis and activation of proliferation pathways in multiple cancers. Discussion We established a prognostic model related to Treg infiltration and this model can be used to establish a clinically relevant classification of TNBC progression. Additionally, our work revealed the underestimable potential of TK1 as a tumor biomarker and immunotherapeutic target.
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Affiliation(s)
- Pengfei Huang
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Xinyue Zhou
- Graduate School, Tianjin Medical University, Tianjin, China
| | - Minying Zheng
- Department of Pathology, Tianjin Union Medical Center, Tianjin, China
| | - Yongjun Yu
- Department of Pathology, Tianjin Union Medical Center, Tianjin, China
| | - Gongsheng Jin
- Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Shiwu Zhang
- Department of Pathology, Tianjin Union Medical Center, Tianjin, China
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15
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Zhang X, Qin H, Tan X, Mo Y, Li Z, Huang G, Wei Z. Predictive value of monocyte to high-density lipoprotein cholesterol ratio and tumor markers in colorectal cancer and their relationship with clinicopathological characteristics. World J Surg Oncol 2023; 21:200. [PMID: 37420210 DOI: 10.1186/s12957-023-03079-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 06/14/2023] [Indexed: 07/09/2023] Open
Abstract
OBJECTIVE To evaluate the predictive value of monocyte (M) to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) and tumor markers in colorectal cancer (CRC) and their correlation with clinicopathological characteristics. METHODS Hematology test data and medical records of 202 CRC patients and 201 healthy subjects were collected retrospectively. The diagnostic efficacy of MHR was evaluated using receiver operating characteristic (ROC) curves and risk factors for CRC were analyzed by multivariate logistic regression. RESULTS CRC patients had significantly higher M, MHR, carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) levels, but significantly lower HDL-C levels than healthy controls (all P < 0.05). Additionally, MHR was positively correlated with tumor differentiation in CRC patients (P = 0.049); CEA and CA199 levels in CRC patients increased with increased stage, lymph node metastasis and tumor size ≥ 5 cm (all P < 0.05). Furthermore, high levels of MHR, CA199 and CEA were independent risk factors for CRC. The area under ROC curve of MHR combined with CEA and CA199 was 0.882/0.869 for the diagnosis of CRC, respectively. CONCLUSION This is the first study to explore the predictive value of MHR in CRC, and its continuous increase is an independent risk factor for CRC. MHR is a promising predictor for CRC progression along with CA199 and CEA.
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Affiliation(s)
- Xuan Zhang
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Hongyan Qin
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Xiaodan Tan
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Yuncong Mo
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhenyong Li
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Guofeng Huang
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China
| | - Zhixiao Wei
- Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.
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16
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Han G, Sun C, Cui L, Huang Y, Yu L, Liu S, Tao M. Efficacy of the low dose apatinib plus deep hyperthermia as third-line or later treatment in HER-2 negative advanced gastric cancer. Pathol Oncol Res 2023; 29:1611114. [PMID: 37465317 PMCID: PMC10350525 DOI: 10.3389/pore.2023.1611114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 06/21/2023] [Indexed: 07/20/2023]
Abstract
Aim: To observe the efficacy of the low dose apatinib plus deep hyperthermia as third-line or later treatment for patients with human epidermal growth factor receptor 2 (HER-2) negative advanced gastric cancer. Methods: 80 eligible patients with HER-2 negative advanced gastric cancer admitted to Jingjiang People's Hospital Affiliated with Yangzhou University-from March 2021 to March 2022 were selected, and they were divided into the control group (n = 40, apatinib) and experimental group (n = 40, apatinib plus deep hyperthermia) on the basis of random number table method. The levels of serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and vascular endothelial growth factor (VEGF) were monitored, and the efficacy of the two groups was analyzed by referring to Karnofsky performance status (KPS), overall survival (OS) and disease control rate (DCR) before and after treatment. Results: The levels of CEA, CA199, and VEGF in both groups were lower after treatment than before (p < 0.05), and lower (CEA: 8.85 ± 1.36 vs. 12.87 ± 1.23, CA199: 34.19 ± 4.68 vs. 50.11 ± 5.73, VEGF: 124.8 ± 18.03 vs. 205.9 ± 19.91) in the experimental group than in the control group (p < 0.05). The DCR and KPS of the patients in the experimental group were significantly higher (DCR: 62.50% vs. 40.00%; KPS: 83.25 ± 1.15 vs. 76.25 ± 1.17) than in the control group (p < 0.05). In survival analysis, patients with control group had shorter OS than the experimental group. (median 5.65 vs. 6.50 months; hazard ratio [HR], 1.63 [95% confidence interval (CI) 1.02-2.60], p = 0.0396). Conclusion: The application of low-dose apatinib plus deep hyperthermia for patients with HER-2 negative gastric cancer who failed second-line treatment should be a promising option.
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Affiliation(s)
- Guohu Han
- Department of Oncology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
- Department of Oncology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu, China
| | - Changchun Sun
- Department of Oncology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu, China
| | - Lihua Cui
- Department of Oncology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu, China
| | - Yufeng Huang
- Department of Oncology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu, China
| | - Lijiang Yu
- Department of Oncology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu, China
| | - Shenzha Liu
- Department of Oncology, Jingjiang People’s Hospital, The Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu, China
| | - Min Tao
- Department of Oncology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
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Dang Y, Dai L, Xu J, Zhou W, Xu Y, Ji G. tRNA-derived fragments are promising biomarkers for screening of early colorectal cancer. MedComm (Beijing) 2023; 4:e227. [PMID: 37153112 PMCID: PMC10156994 DOI: 10.1002/mco2.227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 02/07/2023] [Accepted: 02/08/2023] [Indexed: 05/09/2023] Open
Affiliation(s)
- Yanqi Dang
- Institute of Digestive DiseasesLonghua HospitalChina‐Canada Center of Research for Digestive Diseases (ccCRDD)Shanghai University of Traditional Chinese MedicineShanghaiChina
| | - Liang Dai
- Institute of Digestive DiseasesLonghua HospitalChina‐Canada Center of Research for Digestive Diseases (ccCRDD)Shanghai University of Traditional Chinese MedicineShanghaiChina
- Clinical Research AcademyPeking University Shenzhen HospitalPeking UniversityShenzhenChina
| | - Jingjuan Xu
- Institute of Digestive DiseasesLonghua HospitalChina‐Canada Center of Research for Digestive Diseases (ccCRDD)Shanghai University of Traditional Chinese MedicineShanghaiChina
| | - Wenjun Zhou
- Institute of Digestive DiseasesLonghua HospitalChina‐Canada Center of Research for Digestive Diseases (ccCRDD)Shanghai University of Traditional Chinese MedicineShanghaiChina
| | - Yangxian Xu
- Department of General SurgeryLonghua HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Guang Ji
- Institute of Digestive DiseasesLonghua HospitalChina‐Canada Center of Research for Digestive Diseases (ccCRDD)Shanghai University of Traditional Chinese MedicineShanghaiChina
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18
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Qasemi Rad M, Pouresmaeil V, Hosseini Mojahed F, Amirabadi A, Aalami AH. Clinicopathological utility of miR-203a-3p in diagnosing colorectal cancer. Mol Biol Rep 2022; 49:6975-6985. [PMID: 35511316 DOI: 10.1007/s11033-022-07465-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 04/08/2022] [Indexed: 01/06/2023]
Abstract
BACKGROUND Biomarkers, such as microRNAs, are helpful in diagnosing colorectal cancer, regulating disease progression, predicting disease recurrence, and determining therapy success. This research aimed to look at the clinicopathological characteristics of serum miRNA-203a-3p expression in colorectal cancer patients. METHODS AND RESULTS This case-control study was conducted on 43 patients with colorectal cancer and 43 healthy individuals. After RNA extraction, cDNA was synthesized. The expression of miR-203a-3p was measured using RT-qPCR. Demographic and histochemical data were extracted from patient documents. SPSS and GraphPad Prism software were used to analyze the data. The expression of miR-203a-3p in CRC patients was 2.39 times lower than in the control group (p < 0.0001). The miR-203a-3p expression was significantly lower in the CRC tumor stages, tumor grades, and lymph node metastasis compared to the control group (p < 0.0001 each). The ROC curves showed that the AUC was 0.73, and the best cut-point based on the Youden index was 0.3954, 0.7105, 0.5087, and 0.4868 for detecting colorectal cancer (p = 0.0002), tumor grade (p = 0.006), tumor stage (p = 0.001), and lymph node metastasis (p = 0.0011) compared to the control group, respectively. The binary logistic regression analysis was performed on the correlation between BMI, smoking, and cancer inheritance with miR-203a-3p in cancer and control groups. CONCLUSION This study's findings revealed that serum miR-203a-3p is a fair non-invasive molecular biomarker for diagnosing and progressing tumor grade, tumor stage, and lymph node metastasis in colorectal cancer. However, further research with higher statistical numbers is needed to strengthen the correlation and be used for diagnostic applications.
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Affiliation(s)
- Mahdi Qasemi Rad
- Department of Biology, Mashhad Branch, Islamic Azad University, P.O. Box: 91871-47578, Mashhad, Iran
| | - Vahid Pouresmaeil
- Department of Biochemistry, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran.
- Faculty of Medicine, Mashhad Medical Sciences, Innovative Medical Research Center, Islamic Azad University, Mashhad, Iran.
| | - Fatemeh Hosseini Mojahed
- Department of Internal Medicine, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
| | - Amir Amirabadi
- Department of Internal Medicine, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran
- Radiation Oncology Department, Reza Radiotherapy and Oncology Center, Mashhad, Iran
| | - Amir Hossein Aalami
- Department of Biology, Mashhad Branch, Islamic Azad University, P.O. Box: 91871-47578, Mashhad, Iran.
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Xu S, Liu D, Cui M, Zhang Y, Zhang Y, Guo S, Zhang H. Identification of Hub Genes for Early Diagnosis and Predicting Prognosis in Colon Adenocarcinoma. BIOMED RESEARCH INTERNATIONAL 2022; 2022:1893351. [PMID: 35774271 PMCID: PMC9239823 DOI: 10.1155/2022/1893351] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 06/01/2022] [Indexed: 02/07/2023]
Abstract
Colon adenocarcinoma (COAD) is among the most common digestive system malignancies worldwide, and its pathogenesis and gene signatures remain unclear. This study explored the genetic characteristics and molecular mechanisms underlying colon cancer development. Three gene expression data sets were obtained from the Gene Expression Omnibus (GEO) database. GEO2R was used to determine differentially expressed genes (DEGs) between COAD and normal tissues. Then, the intersection of the data sets was obtained. Metascape was used to perform the functional enrichment analyses. Next, STRING was used to build protein-protein interaction (PPI) networks. Hub genes were identified and analysed using Cytoscape. Next, survival analysis and expression analysis of the hub genes were performed. ROC curve analysis was performed for further test of the diagnostic efficacy. Finally, alterations in the hub genes were predicted and analysed by cBioPortal. Altogether, 436 DEGs were detected. The DEGs were mainly enriched in cell cycle phase transition, nuclear division, meiotic nuclear division, and cytokinesis. Based on PPI networks, 20 hub genes were selected. Among them, 6 hub genes (CCNB1, CCNA2, AURKA, NCAPG, DLGAP5, and CENPE) showed significant prognostic value in colon cancer (P < 0.05), while 5 hub genes (CDK1, CCNB1, CCNA2, MAD2L1, and DLGAP5) were associated with early colon cancer diagnosis and ROC curve analysis showed good diagnostic accuracy. In conclusion, integrated bioinformatics analysis was used to identify hub genes that reveal the potential mechanism of carcinogenesis and progression of colon cancer. The hub genes might be novel biomarkers for early diagnosis, treatment, and prognosis of colon cancer.
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Affiliation(s)
- Shuo Xu
- Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China
| | - Dingsheng Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China
| | - Mingming Cui
- Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China
| | - Yao Zhang
- Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China
| | - Yu Zhang
- Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China
| | - Shiqi Guo
- Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China
| | - Hong Zhang
- Department of General Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang 110004, China
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20
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Liu D, Xu Y, Fang Y, Hu K. Development of a Novel Immune-Related Gene Signature to Predict Prognosis and Immunotherapeutic Efficiency in Gastric Cancer. Front Genet 2022; 13:885553. [PMID: 35692814 PMCID: PMC9186121 DOI: 10.3389/fgene.2022.885553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 04/25/2022] [Indexed: 11/30/2022] Open
Abstract
Background: Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of tumor-related deaths globally. Herein, we attempted to build a novel immune-related gene (IRG) signature that could predict the prognosis and immunotherapeutic efficiency for GC patients. Methods: The mRNA transcription data and corresponding clinical data of GC were downloaded from The Cancer Genome Atlas (TCGA) database as the training group and the GSE84437 data set as the testing cohort, followed by acquisition of IRGs from the InnateDB resource and ImmPort database. Using the univariate Cox regression analysis, an IRG signature was developed. Several immunogenomic analyses were performed to illustrate the associations between the immune risk score and tumor mutational burden, immune cell infiltrations, function of immune infiltration, clinical characteristics, immune subtype, and immunotherapeutic response. Results: The analysis of 343 GC samples and 30 normal samples from the TCGA database gave rise to 8,713 differentially expressed genes (DEGs) and 513 differentially expressed immune-related genes (DEIRGs) were extracted. The novel IRG signature contained eight DEIRGs (FABP4, PI15, RNASE2, CGB5, INHBE, RLN2, DUSP1, and CD36) and was found to serve as an independent predictive and prognostic factor for GC. Then, the GC patients were separated into the high- and low-risk groups based on the median risk score, wherein the low-risk group presented a better prognosis and was more sensitive to immunotherapy than did the high-risk group. According to the time-dependent ROC curves and AUCs, the immunotherapeutic value of the signature was better than the Tumor Immune Dysfunction and Exclusion (TIDE) and T-cell inflammatory signature (TIS) scores. In addition, the AUCs of the risk score for predicting 1-, 2-, and 3-year OS were 0.675, 0.682, and 0.710, respectively, which indicated that the signature had great predictive power. Conclusion: This study presents a novel IRG signature based on the tumor immune microenvironment, which could improve the prediction of the prognosis and immunotherapeutic efficiency for GC patients. The powerful signature may serve as novel biomarkers and provide therapeutic targets for precision oncology in clinical practice.
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Affiliation(s)
- Dongliang Liu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yuanmin Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yu Fang
- Department of General Surgery, The First Hospital Affiliated to the University of Science and Technology of China, Hefei, China
- *Correspondence: Yu Fang, ; Kongwang Hu,
| | - Kongwang Hu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Yu Fang, ; Kongwang Hu,
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21
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Ng SS, Lee HL, Pandian BR, Doong RA. Recent developments on nanomaterial-based optical biosensor as potential Point-of-Care Testing (PoCT) probe in carcinoembryonic antigen detection: A review. Chem Asian J 2022; 17:e202200287. [PMID: 35471591 DOI: 10.1002/asia.202200287] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/25/2022] [Indexed: 11/09/2022]
Abstract
For the past decades, several cancer biomarkers have been exploited for rapid and accurate prognosis or diagnosis purposes. In this review, the optical biosensor is targeted for carcinoembryonic antigen (CEA) detection. The CEA level is a prominent parameter currently used in clinical cases for the prognosis of cancer-related diseases. Many nanomaterial-based biosensors are invented as alternatives for the commonly used enzyme-linked immunosorbent assays (ELISA) immunoassay method in CEA detection as the traditional approach but they possess certain drawbacks such as tedious procedure, high technical demand, and costly. Nevertheless, the effort appears to be wasted as none of them are being actualised. Generally, the sensor function was carried out by converting bio-signals generated upon the interface of the receptor into light signals. These sensors were popular due to specific advantages such as sensitivity, being free from chemical and electromagnetic interferences, wide dynamic range, and being easy to be monitored. The features of PoC diagnostics are discussed and associated with the various applications of colorimetric-based and chemiluminescent-based biosensors. The roles of nanomaterials in each application were also summarised by comparing the modification, incubation period, lowest detection limit (LOD) and linear range of detection amount. The challenges and future perspectives were highlighted at the end of the review.
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Affiliation(s)
- Siew Suan Ng
- National Tsing Hua University, Department of Analytical and Environmental Science, TAIWAN
| | - Hooi Ling Lee
- Universiti Sains Malaysia, School of Chemical Sciences, School of Chemical Sciences,, Universiti Sains Malaysia,, 11800, USM, MALAYSIA
| | | | - Ruey-An Doong
- National Tsing Hua University, Department of Analytical and Environmental Science, TAIWAN
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22
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Fu J, Tu M, Zhang Y, Zhang Y, Wang J, Zeng Z, Li J, Zeng F. A model of multiple tumor marker for lymph node metastasis assessment in colorectal cancer: a retrospective study. PeerJ 2022; 10:e13196. [PMID: 35433129 PMCID: PMC9009328 DOI: 10.7717/peerj.13196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 03/09/2022] [Indexed: 02/05/2023] Open
Abstract
Background Assessment of colorectal cancer (CRC) lymph node metastasis (LNM) is critical to the decision of surgery, prognosis, and therapy strategy. In this study, we aimed to develop and validate a multiple tumor marker nomogram for predicting LNM in CRC patients. Methods A total of 674 patients who met the inclusion criteria were collected and randomly divided into primary cohort and internal test cohort at a ratio of 7:3. An external test cohort enrolled 178 CRC patients from the West China Hospital. Clinicopathologic variables were obtained from electronic medical records. The least absolute shrinkage and selection operator (LASSO) and interquartile range analysis were carried out for variable dimensionality reduction and feature selection. Multivariate logistic regression analysis was conducted to develop predictive models of LNM. The performance of the established models was evaluated by the receiver operating characteristic (ROC) curve, calibration belt, and clinical usefulness. Results Based on minimum criteria, 18 potential features were reduced to six predictors by LASSO and interquartile range in the primary cohort. The model demonstrated good discrimination and ROC curve (AUC = 0.721 in the internal test cohort, AUC = 0.758 in the external test cohort) in LNM assessment. Good calibration was shown for the probability of CRC LNM in the internal and external test cohorts. Decision curve analysis illustrated that multi-tumor markers nomogram was clinically useful. Conclusions The study proposed a reliable nomogram that could be efficiently and conveniently utilized to facilitate the assessment of individually-tailored LNM in patients with CRC, complementing imaging and biopsy tests.
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Affiliation(s)
- Jiangping Fu
- Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan, China,National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Guangxi Zhuang Autonomous Region, China,Department of Oncology, Dazhou Central Hospital, Dazhou, Sichuan, China
| | - Mengjie Tu
- Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan, China
| | - Yin Zhang
- Department of Oncology, Dazhou Central Hospital, Dazhou, Sichuan, China
| | - Yan Zhang
- Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Sichuan, China
| | - Jiasi Wang
- Department of Clinical Laboratory, Dazhou Central Hospital, Dazhou, Sichuan, China
| | - Zhaoping Zeng
- Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan, China
| | - Jie Li
- Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan, China
| | - Fanxin Zeng
- Department of Clinical Research Center, Dazhou Central Hospital, Dazhou, Sichuan, China
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23
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Hong X, Wang G, Liu X, Wu M, Zhang X, Hua X, Jiang P, Wang S, Tang S, Shi X, Huang Y, Shen T. Lipidomic biomarkers: Potential mediators of associations between urinary bisphenol A exposure and colorectal cancer. JOURNAL OF HAZARDOUS MATERIALS 2022; 427:127863. [PMID: 34848068 DOI: 10.1016/j.jhazmat.2021.127863] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 10/25/2021] [Accepted: 11/18/2021] [Indexed: 06/13/2023]
Abstract
Previous research reported associations between bisphenol A (BPA) exposure and some malignant tumor incidences, yet the underlying mechanism remains largely uncertain. This investigation was aimed to explore the association of BPA exposure burden with colorectal cancer (CRC) and the role of tumor tissue lipid metabolism in the associations between BPA and CRC using lipidomic approach. Urinary BPA levels in CRC cases were significantly higher than those in controls (P value < 0.05). BPA was positively correlated with all three serum CRC biomarkers, with an estimated odds ratio (OR) of 4.45 (95% confidence interval (95% CI): [1.31, 15.14]) between the highest and lowest tertiles of exposure. Lipidomic screening of tumor samples suggested significant perturbation in the glycerophospholipid metabolism pathway, of which phosphatidylcholine (PC 34:0), phosphatidylcholine (PC 37:1), phosphatidylethanolamine (PE 34:2), triacylglycerol (TG 56:4) demonstrated mediation contribution of 21.9%, 18.7%, 18.4% and 27.39%, respectively, in the association between BPA exposure and CRC. Our work provides novel findings that cancer tissue metabolites may be playing vital mediating roles in the associations between BPA exposure burden and CRC risk. These findings contribute to better understanding of the etiology of CRC induced by environmental stressors.
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Affiliation(s)
- Xu Hong
- Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Gengfu Wang
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, PR China
| | - Xingcun Liu
- Department of Gastrointestinal surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Ming Wu
- Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Xindong Zhang
- Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Xiaohui Hua
- Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Pengpeng Jiang
- Department of Gastrointestinal surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230032, Anhui, PR China
| | - Sheng Wang
- The Center for Scientific Research of Anhui Medical University, Hefei 230032, Anhui Province, PR China
| | - Song Tang
- National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, PR China
| | - Xiaoming Shi
- National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, PR China
| | - Yichao Huang
- Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, PR China.
| | - Tong Shen
- Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, PR China.
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Zuo S, Wang H, Li L, Pan H, Lu L. Thymidine Kinase 1 Drives Skin Cutaneous Melanoma Malignant Progression and Metabolic Reprogramming. Front Oncol 2022; 12:802807. [PMID: 35311151 PMCID: PMC8927676 DOI: 10.3389/fonc.2022.802807] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 01/17/2022] [Indexed: 11/15/2022] Open
Abstract
Background Thymidine kinase 1 (TK1) is a cell cycle-dependent kinase that catalyzes the addition of a gamma-phosphate group to thymidine. The protumorigenic role of TK1 has been reported in various malignancies. However, the role of TK1 in skin cutaneous melanoma (SKCM) remains unclear. This study aimed to explore the molecular function of TK1 in SKCM progression. Methods Bioinformatics data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Subcutaneous xenografts were established to observe the effect of TK1 knockdown on the proliferation of SKCM cells in vivo. RNA sequencing (RNA-seq; deposited in Sequence Read Archive, SRX10950283-SRX10950285 for A375 control cells and SRX10950286-SRX10950288 for TK1-silenced A375 cells) and immunoprecipitation–mass spectrometry (IP-MS) were used to analyze TK1-related genes and pathways. Seahorse XF Cell Mito tests and glycolysis stress assays were conducted for metabolic testing. Results TK1 was upregulated in malignant SKCM compared to that in normal tissues and cell lines. Elevated expression of TK1 was associated with poor prognosis. In vitro and in vivo assays demonstrated that TK1 promoted the proliferation and migration of SKCM cells. Moreover, TK1 was strongly associated with multiple intracellular metabolic pathways, facilitating cell mitochondrial respiration and glycolysis in SKCM malignant progression. Conclusions TK1 drives SKCM malignant progression and supports metabolic reprogramming, indicating that TK1 serves as a therapeutic target for SKCM.
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Affiliation(s)
- Sipeng Zuo
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Huixue Wang
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Lin Li
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Hui Pan
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
| | - Linna Lu
- Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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Cai Q, Zhu M, Duan J, Wang H, Chen J, Xiao Y, Wang Y, Wang J, Yu X, Yang H. Comprehensive Analysis of Immune-Related Prognosis of TK1 in Hepatocellular Carcinoma. Front Oncol 2022; 11:786873. [PMID: 35127491 PMCID: PMC8814100 DOI: 10.3389/fonc.2021.786873] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 12/22/2021] [Indexed: 12/12/2022] Open
Abstract
Increased expression of TK1 is associated with the progression of a variety of tumors. However, the relationship of TK1 expression with immune cell infiltration and its prognostic value in hepatocellular carcinoma (HCC) are still unknown. In this study the TCGA database was used to evaluate TK1 expression and its impact on survival in patients with HCC. Compared with normal tissue, TK1 in the liver tissue of patients with HCC was significantly up-regulated at both the mRNA and protein levels. Furthermore, TK1 expression was significantly related to pathological stage, tumor stage and lymph node metastasis, with high TK1 expression being an unfavorable prognostic factor for HCC. TK1 expression was also significantly associated with the infiltration of B cells, T cells, and dendritic cells in HCC. Single-cell sequencing analysis revealed that TK1 was associated with relatively large changes in T cells, especially gamma-delta T cells. A prognostic risk score based on TK1-related immune genes (CD40LG and TNFRSF4) was established using COX regression analysis. By integrating the immune-related risk score model with clinical features, a nomogram was constructed to predict the survival rate of HCC patients (1 year, 3-year and 5-year AUC of 0.782, 0.783 and 0.771, respectively). Knockdown of the target gene for TK1 was found to have significant anti-apoptosis and pro-proliferation effects on HepG2 cells. The level of TK1 in the serum and liver tissue of patients with HCC was significantly increased relative to healthy controls. These findings highlight the role of TK1 in the tumor immune response of HCC patients and in the proliferation and apoptosis of HepG2 cells. TK1 could therefore be a potential immunotherapy target for HCC patients, while the two immune genes related to TK1 (CD40LG And TNFRSF4) may be promising prognostic biomarkers in HCC.
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Affiliation(s)
- Qun Cai
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
- *Correspondence: Qun Cai,
| | - Mingyan Zhu
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Jinnan Duan
- Department of Infectious Diseases, Shaoxing People’s Hospital, Shaoxing, China
| | - Hao Wang
- Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jingdan Chen
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Yixin Xiao
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Yangqin Wang
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Jianfang Wang
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Xuewen Yu
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
| | - Hui Yang
- Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, Affiliated Lihuili Hospital of Ningbo University, Ningbo, China
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Zhu C, Zhang N, Zhong A, Xiao K, Lu R, Guo L. A combined strategy of TK1, HE4 and CA125 shows better diagnostic performance than risk of ovarian malignancy algorithm (ROMA) in ovarian carcinoma. Clin Chim Acta 2022; 524:43-50. [PMID: 34813778 DOI: 10.1016/j.cca.2021.11.018] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 10/19/2021] [Accepted: 11/17/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND The dual marker algorithm Risk of Ovarian Malignancy Algorithm (ROMA) has been widely used in the clinic for the identification of equivocal pelvic masses in ovarian carcinoma. To obtain higher diagnostic efficiency, we created a new diagnostic index, Risk of Ovarian Malignancy Index (ROMI), by combing thymidine kinase 1 (TK1), HE4 and CA125. METHODS 335 patients with pelvic masses on imaging and 46 healthy controls were enrolled. Serum TK1 was analyzed before further study. ROMI and ROMA were evaluated for diagnostic efficiency. RESULTS The level of TK1 was elevated in malignant ovarian tumors compared to benign masses (p < 0.001) and healthy controls (p < 0.001). TK1 expression was positively correlated with stage, intrapelvic metastasis, lymphatic metastasis and distant metastasis (all p values < 0.001). The area under the receiver operating characteristic curve (AUC) of ROMI was higher than that of ROMA for both pre- and postmenopausal women. ROMI had better sensitivity, specificity, accuracy, and positive and negative predictive values than ROMA in diagnosis of all-stage or stage I + II ovarian carcinoma for both pre- and postmenopausal women. CONCLUSIONS TK1 is a potential biomarker in detection of ovarian carcinoma. ROMI shows better diagnostic performance than ROMA in distinguishing malignant ovarian tumors from benign masses.
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Affiliation(s)
- Cheng Zhu
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Nenghua Zhang
- Department of Clinical Laboratory, Municipal Key-Innovative Discipline of Molecular Diagnostics, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China
| | - Ailing Zhong
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Kangjia Xiao
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Renquan Lu
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Lin Guo
- Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Lv J, Liu YY, Jia YT, He JL, Dai GY, Guo P, Zhao ZL, Zhang YN, Li ZX. A nomogram model for predicting prognosis of obstructive colorectal cancer. World J Surg Oncol 2021; 19:337. [PMID: 34857001 PMCID: PMC8638364 DOI: 10.1186/s12957-021-02445-6] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 10/23/2021] [Indexed: 02/07/2023] Open
Abstract
Background The prognosis of obstructive colorectal cancer (oCRC) is worse than that of nonobstructive colorectal cancer. However, no previous study has established an individualized prediction model for the prognosis of patients with oCRC. We aimed to screen the factors that affect the prognosis of oCRC and to use these findings to establish a nomogram model that predicts the individual prognosis of patients with oCRC. Methods This retrospective study collected data of 181 patients with oCRC from three medical hospitals between February 2012 and December 2017. Among them, 129 patients from one hospital were used as the training cohort. Univariate and multivariate analyses were used in this training cohort to select independent risk factors that affect the prognosis of oCRC, and a nomogram model was established. The other 52 patients from two additional hospitals were used as the validation cohort to verify the model. Results Multivariate analysis showed that carcinoembryonic antigen level (p = 0.037, hazard ratio [HR] = 2.872 [1.065–7.740]), N stage (N1 vs. N0, p = 0.028, HR = 3.187 [1.137–8.938]; N2 vs. N0, p = 0.010, HR = 4.098 [1.393–12.051]), and surgical procedures (p = 0.002, HR = 0.299 [0.139–0.643]) were independent prognostic factors of overall survival in patients with oCRC. These factors were used to construct the nomogram model, which showed good concordance and accuracy. Conclusion Carcinoembryonic antigen, N stage, and surgical method are independent prognostic factors for overall survival in patients with oCRC, and the nomogram model can visually display these results.
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Affiliation(s)
- Jian Lv
- Department of Emergency, Hebei General Hospital, No. 348 Heping West Road, Shijiazhuang, 050051, Hebei, China
| | - Yuan Yuan Liu
- Department of Anorectal Surgery, Huanghua General Hospital, No. 262 Xinhua Road, Huanghua, 061100, Hebei, China
| | - Yi Tao Jia
- Department of Oncology, Hebei General Hospital, Shijiazhuang, 050051, Hebei, China
| | - Jing Li He
- Second Department of Surgery, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
| | - Guang Yao Dai
- Department of Anorectal Surgery, The First Hospital of Shijiazhuang, No. 36, Fanxi Road, Shijiazhuang, 050011, Hebei, China
| | - Peng Guo
- Department of Plastic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
| | - Zhao Long Zhao
- Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China
| | - Yan Ni Zhang
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Zhong Xin Li
- Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, No. 89 Donggang Road, Shijiazhuang, 050000, Hebei, China.
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Verma R, Sharma PC. Identification of stage-specific differentially expressed genes and SNPs in gastric cancer employing RNA-Seq based transcriptome profiling. Genomics 2021; 114:61-71. [PMID: 34839019 DOI: 10.1016/j.ygeno.2021.11.032] [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: 10/31/2019] [Accepted: 11/23/2021] [Indexed: 12/24/2022]
Abstract
We analysed over 400 million reads obtained from Illumina sequencing of six pairs of libraries representing two each of stage I, II, and III gastric tumors and corresponding normal tissues to identify differentially expressed genes (DEGs), single nucleotide polymorphisms (SNPs), and transcription factors (TFs). In total, 2207 DEGs including 972 upregulated genes and 1235 downregulated genes were detected. Of these, several stage-specific signature genes were identified. The protein-protein interaction networks involving DEGs and TFs were constructed. The KEGG pathway analysis of SNP harbouring genes revealed their involvement in different cancer related pathways like apoptosis, mTOR pathway, and MAPK signaling pathway. The SNP analysis showed implication of host genes in GO categories like immune system process, regulation of signaling, response to stress, and transport. A biased chromosomal distribution of DEGs and SNP harbouring genes was observed. Our study would provide further insights into the complex regulatory mechanisms operating during gastric tumorigenesis.
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Affiliation(s)
- Renu Verma
- University School of Biotechnology, Guru Gobind Singh Indraprastha University, New Delhi, India
| | - Prakash Chand Sharma
- University School of Biotechnology, Guru Gobind Singh Indraprastha University, New Delhi, India.
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29
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Liang L, Fang J, Han X, Zhai X, Song Y, Lu Y, Zhang Q, Ma R. Prognostic Value of CEA, CA19-9, CA125, CA724, and CA242 in Serum and Ascites in Pseudomyxoma Peritonei. Front Oncol 2021; 11:594763. [PMID: 34733775 PMCID: PMC8558433 DOI: 10.3389/fonc.2021.594763] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 09/20/2021] [Indexed: 12/27/2022] Open
Abstract
Purpose To investigate the expression of carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), CA19-9, CA724, and CA242 in serum and ascites of pseudomyxoma peritonei (PMP) patients and evaluate the predictive value of these elevated biomarkers in pathological grade, completeness of cytoreduction (CC), and survival. Methods From May 2009 to October 2019, a total of 512 patients diagnosed with PMP through pathology in Aerospace Center Hospital were enrolled. The serum and ascites tumor biomarkers were obtained. The diagnostic values between serum and ascites biomarkers in pathology and CC were compared by the receiver operating characteristic (ROC) curves. The correlation between pathology, cytoreduction, and biomarkers was calculated by univariate and multivariate logistic regression. The associations between different numbers of elevated biomarkers and survival status were examined using univariate and multivariate backward Cox proportional hazard regression models. Results The results showed that the areas under the ROC curves (AUROC) in the diagnosis of CC were 0.798 (95% CI: 0.760-0.836) and 0.632 (95% CI: 0.588-0.676) in serum and ascites biomarkers, respectively. The elevated serum and ascites biomarkers were independent risk factors for both pathology and CC. The 1-year, 3-year, and 5-year survival rates were 89.07%, 73.22%, and 66.94%, respectively. Longer survival was observed in patients who had less than two elevated serum biomarkers compared with those with 2-3 and 4-5 elevated serum biomarkers (p < 0.001). Conclusion CEA, CA125, CA19-9, CA724, and CA242 in serum and ascites can be used to judge the severity and predict the resectability. Furthermore, different numbers of elevated biomarkers can help determine the prognosis of PMP.
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Affiliation(s)
- Lei Liang
- Department of Ultrasound, Aerospace Center Hospital, Beijing, China
| | - Jingyang Fang
- Department of Ultrasound, Aerospace Center Hospital, Beijing, China
| | - Xuedi Han
- Department of Ultrasound, Aerospace Center Hospital, Beijing, China
| | - Xichao Zhai
- Department of Myxoma, Aerospace Center Hospital, Beijing, China
| | - Yan Song
- Department of Clinical Laboratory, Aerospace Center Hospital, Beijing, China
| | - Yiyan Lu
- Department of Pathology, Aerospace Center Hospital, Beijing, China
| | - Qian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ruiqing Ma
- Department of Myxoma, Aerospace Center Hospital, Beijing, China
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Liu H, Gu H, Kutbi EH, Tan SC, Low TY, Zhang C. Association of IGF-1 and IGFBP-3 levels with gastric cancer: A systematic review and meta-analysis. Int J Clin Pract 2021; 75:e14764. [PMID: 34469629 DOI: 10.1111/ijcp.14764] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 07/22/2021] [Accepted: 08/10/2021] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Many studies have investigated the association between serum IGF-1 and IGFBP levels with gastric cancer (GC), but the results remained inconclusive. In this work, we performed a systematic review and meta-analysis to examine the precise association of serum levels of IGF-1 and IGFBP with GC. METHODS A comprehensive systematic search was carried out in PubMed/MEDLINE, SCOPUS, Web of Science, and EMBASE databases for (nested) case-control studies that reported the levels of IGF-1 and IGFBP in GC cases and healthy controls, from inception until October 2020. Weighted mean difference (WMD) was calculated for estimating combined effect size. Subgroup analysis was performed to identify the source of heterogeneity among studies. RESULTS We found eight and five eligible studies (with 1541 participants) which provided data for IGF-1 and IGFBP, respectively. All studies on IGFBP reported the IGFBP-3 isoform. The pooled results indicate that GC patients had significantly lower serum IGF-1 [WMD = -26.21 ng/mL (95% CI, -45.58 to -6.85; P = .008)] and IGFBP-3 [WMD = -0.41 ng/mL (95% CI, -0.80 to -0.01; P = .04; I2 = 89.9%; P < .001)] levels than those in healthy subjects. Significant heterogeneity was observed in the association, which could be attributed to the sample size of the studies. CONCLUSIONS In conclusion, our study reveals a significantly lower level of IGF-1 and IGFBP-3 in GC patients compared with healthy control subjects.
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Affiliation(s)
- Hongyu Liu
- Department of Pathology, Qiqihar Hospital Affiliated to Southern Medical University, Qiqihar, China
| | - Huxia Gu
- Department of Network Information, Fuling Central Hospital of Chongqing city, Chongqing, China
| | - Emad H Kutbi
- Biorepository Department, Biomedical Research Administration, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Shing Cheng Tan
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Teck Yew Low
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Chong Zhang
- Department of Pathology, Fuling Central Hospital of Chongqing city, Chongqing, China
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Clinical Value of Serum Thrombospondin-2 Combined with CA19-9 in Early Diagnosis of Gastric Cancer. JOURNAL OF ONCOLOGY 2021; 2021:2483964. [PMID: 34659407 PMCID: PMC8516522 DOI: 10.1155/2021/2483964] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/14/2021] [Accepted: 09/15/2021] [Indexed: 11/20/2022]
Abstract
Gastric cancer (GC) is a kind of common cancer worldwide. Too late in diagnosis results in poor prognosis of patients with GC. Thrombospondin-2 (THBS2) is a type of secreted protein that has been found to be a diagnostic biomarker in a variety of cancers. Our study aimed to uncover the clinical value of THBS2 in early detection for patients with gastric cancer. THBS2 was upregulated in gastric cancer tissue compared with normal tissue via analyzing data obtained from The Cancer Genome Atlas (TCGA) database. Additionally, the enzyme-linked immunosorbent assay revealed that the level of serum THBS2 and carcinoembryonic antigen, CA19-9, was higher dramatically in patients with early gastric cancer (EGC) than that in healthy control (HC) in addition to patients with benign gastric tumor (BGT), which suggested that THBS2 indeed associated with GC. Receiver operator characteristic (ROC) curve assay was conducted to demonstrate that serum THBS2 was similar to CA19-9 to distinguish patients with early gastric cancer from healthy control and patients with benign gastric tumor and that THBS2 combined with CA19-9 improved the detective performance of THBS2 for early gastric cancer. Furthermore, we applied the gene set enrichment analysis assay to analyze signaling pathways related to THBS2. We found that THBS2 positively controlled MAPK and WNT signaling pathways, which indicated that THBS2 might exert its functions via the pathway mentioned above. Thus, our study expounded that serum THBS2 could serve as a vital early diagnostic marker for patients with gastric cancer.
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32
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Xu Y, Zhang P, Zhang K, Huang C. The application of CA72-4 in the diagnosis, prognosis, and treatment of gastric cancer. Biochim Biophys Acta Rev Cancer 2021; 1876:188634. [PMID: 34656687 DOI: 10.1016/j.bbcan.2021.188634] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 10/09/2021] [Accepted: 10/10/2021] [Indexed: 02/07/2023]
Abstract
The role of conventional serum tumor marker, carbohydrate antigen 72-4 (CA72-4), in assisting diagnosis, monitoring dynamic progression, and evaluating the prognosis of gastric cancer (GC) should not be ignored, especially in the Chinese population. Even though CA72-4 has been used in clinical practice for decades, its modest positivity rate, sensitivity, and specificity did not meet the high demand of the clinical application. However, over the years, some progress in the functions of CA72-4 has been achieved, suggesting that CA72-4 can still be considered a promising marker in oncology. As a biomarker, CA72-4 can achieve improved sensitivity (SEN) and specificity (SPE) when combined with other biomarkers, selecting suitable reference values, improving detection techniques, and identifying the risk threshold. As a predictor, elevated serum CA72-4 levels were found to be significantly associated with prognostic risk factors, further assessing therapeutic validity and resectability. Recently, an effective method to reduce the toxicity of CA72-4 targeted therapy has been developed. Moreover, CA72-4 could induce novel aptamers to react with tumor cells and enhance the efficacy of trastuzumab in HER2-positive GC. Therefore, in this review, we discuss the most recent application of CA72-4 in the diagnosis, prognosis, and treatment of GC.
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Affiliation(s)
- Yitian Xu
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China
| | - Pengshan Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China
| | - Kundong Zhang
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China
| | - Chen Huang
- Department of Gastrointestinal Surgery, Shanghai General Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200080, PR China.
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O'Neill RS, Stoita A. Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket? World J Gastroenterol 2021; 27:4045-4087. [PMID: 34326612 PMCID: PMC8311531 DOI: 10.3748/wjg.v27.i26.4045] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/24/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis. To combat this, there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma. Currently, serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker. In the search for a biomarker that is both sensitive and specific for the diagnosis of PC, there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC. Currently, promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA (miRNA) in serum and circulating tumour cells. Both these modalities, although in their infancy and yet to be widely accepted into routine clinical practice, possess merit in the early detection of PC. We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC (serum, urinary, salivary, faecal, pancreatic juice and biliary fluid).
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Affiliation(s)
- Robert S O'Neill
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney 2010, Australia
- St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
| | - Alina Stoita
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney 2010, Australia
- St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
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Gong Q, Zhang X, Liang A, Huang S, Tian G, Yuan M, Ke Q, Cai Y, Yan B, Wang J, Wang J. Proteomic screening of potential N-glycoprotein biomarkers for colorectal cancer by TMT labeling combined with LC-MS/MS. Clin Chim Acta 2021; 521:122-130. [PMID: 34242638 DOI: 10.1016/j.cca.2021.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 06/29/2021] [Accepted: 07/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Colorectal cancer (CRC) is part of the most widespread malignant tumors. At present, colonoscopy is a routine procedure in the diagnosis of CRC, but it is traumatic. Carcinoembryonic antigen, CA199, and CA242 are common serum markers for the diagnosis of CRC; however, they do not demonstrate satisfactory specificity and sensitivity for the diagnosis of CRC. Hence, Now it is necessary to screen many valuable serum biomarkers for CRC, proteomics methods have been used to investigate PTMs such as glycosylation of proteins with prominent roles in the occurrence and development of tumors. METHODS This study screens altering glycosylated proteins of CRC tissues using LC-MS/MS quantitative glycoproteomics, and then these candidate biomarkers for CRC are further validated by serum glycoproteomics. RESULTS The results of glycoproteomics in CRC tissues show that the abundance of 160 and 79 glycerogelatin proteins was obviously upregulated and downregulated compared with their adjacent tissues(P < 0.05). Bioinformatics analysis suggests that these molecules are mainly involved in many biological processes, including skeletal system development, collagen fibril organization, and receptor-mediated endocytosis. Results of serum glycoproteomics show that the changing trends of 2 protein glycosylation were consistent with MS results of CRC tissues, including ICAM1and APMAP. Areas under the ROC curve (AUC) results confirm that ICAM1and APMAP as early immune diagnosis markers of CRC has excellent sensitivity and specificity. CONCLUSION The ICAM1 and APMAP may serve as a potential tumor marker for CRC.
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Affiliation(s)
- Qian Gong
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China
| | - Xiuming Zhang
- Medical Laboratory of Shenzhen Luohu People's Hospital, Shenzhen, PR China
| | - Aifeng Liang
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China
| | - Sinian Huang
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China
| | - Guangang Tian
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China
| | - Mengjiao Yuan
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China
| | - Qing Ke
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China
| | - Yijun Cai
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China
| | - Bin Yan
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China
| | - Jin Wang
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China; Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, PR China.
| | - Jinjin Wang
- Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, PR China.
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Xu P, Xu X, Zhang L, Li Z, Qiang J, Yao J, Xu A. hsa_circ_0060975 is highly expressed and predicts a poor prognosis in gastric cancer. Oncol Lett 2021; 22:619. [PMID: 34257727 PMCID: PMC8243078 DOI: 10.3892/ol.2021.12880] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 05/24/2021] [Indexed: 11/23/2022] Open
Abstract
Gastric cancer (GC) is the fifth most common cancer and GC has a high mortality rate worldwide. Circular (circ) RNAs serve an important role in cancer. The present study aimed to investigate the expression level of hsa_circ_0060975 in gastric cancer (GC) and to determine the clinical pathological significance of hsa_circ_0060975 in patients with GC. Reverse transcription-quantitative PCR was used to detect expression level of hsa_circ_0060975 in 192 GC and adjacent non-cancerous gastric tissues, in GC cell lines (MKN-45, HGC27 and AGS) and a human gastric epithelium cell line (GES-1), as well as in plasma samples from 126 patients with GC and 92 healthy volunteers. All plasma and tissue samples of were obtained from The First Affiliated Hospital of Anhui Medical University (Hefei, China). The relationship between hsa_circ_0060975 expression and clinical pathological factors was analyzed using the χ2 test. The diagnostic value of hsa_circ_0060975 was analyzed using the receiver operating characteristic curve (ROC curve), while the Kaplan-Meier method was used to analyze the relationship of hsa_circ_0060975 expression with the survival of patients with GC as determined by log-rank tests. Univariate and multivariate Cox regression analyses were used to identify the prognostic factors, including hsa_circ_0060975 expression and clinical pathological factors. In addition, the potential function of hsa_circ_0060975 was evaluated via bioinformatics analysis. The expression level of hsa_circ_0060975 was higher in GC tissues compared with adjacent non-cancerous gastric tissues, GC cell lines compared with GES-1 and plasma samples from patients with GC compared with plasma samples from healthy volunteers. In addition, higher hsa_circ_0060975 expression was associated with histological grade, pathological stage and tumor (T) classification in GC tissues and plasma samples (P<0.05). The area under the ROC curves of hsa_circ_0060975, the combination with hsa_circ_0060975 and carcinoembryonic antigen (CEA) or CEA alone were 0.804 (sensitivity, 0.746; specificity, 0.783; P<0.001); 0.931 (sensitivity, 0.937; specificity, 0.870; P<0.001) and 0.924 (sensitivity, 0.937; sspecificity, 0.804; P<0.001) respectively. The Kaplan-Meier survival analysis revealed that the overall survival (OS) and disease-free survival (DFS) time of patients with higher hsa_circ_0060975 expression were shorter compared with those in patients with lower hsa_circ_0060975 expression. Univariate and multivariate Cox regression analyses in OS and DFS time determined that the expression level of hsa_circ_0060975, histological grade and pathological stage were independent prognostic factors for patients with GC. In addition, the bioinformatics analysis results suggested that the abnormal expression of hsa_circ_0060975 may serve an important role in tumorigenesis. Hence, hsa_circ_0060975 expression may be an independent prognostic factor for patients with GC and may be a potential marker for biological malignancy.
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Affiliation(s)
- Peng Xu
- Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R. China.,Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
| | - Xiaolan Xu
- Department of Critical Care Medicine, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
| | - Lixiang Zhang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R. China
| | - Zhengnan Li
- Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
| | - Jianjun Qiang
- Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
| | - Jie Yao
- Department of Hepatobiliary and Pancreatic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China
| | - Aman Xu
- Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R. China.,Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R. China
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Druce P, Calanzani N, Snudden C, Milley K, Boscott R, Behiyat D, Martinez-Gutierrez J, Saji S, Oberoi J, Funston G, Messenger M, Walter FM, Emery J. Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Lower Gastrointestinal Cancers: A Systematic Review and Meta-Analysis. Adv Ther 2021; 38:3032-3065. [PMID: 33907946 PMCID: PMC8078393 DOI: 10.1007/s12325-021-01645-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 01/30/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the potential to aid with early detection. Substantial investment has been made into the development of biomarkers; however, studies are often carried out in specialist settings and few have been evaluated for low-prevalence populations. METHODS We aimed to identify novel biomarkers for the detection of lower GI cancers that have the potential to be evaluated for use in primary care. MEDLINE, Embase, Emcare and Web of Science were systematically searched for studies published in English from January 2000 to October 2019. Reference lists of included studies were also assessed. Studies had to report on measures of diagnostic performance for biomarkers (single or in panels) used to detect colorectal or anal cancers. We included all designs and excluded studies with fewer than 50 cases/controls. Data were extracted from published studies on types of biomarkers, populations and outcomes. Narrative synthesis was used, and measures of specificity and sensitivity were meta-analysed where possible. RESULTS We identified 142 studies reporting on biomarkers for lower GI cancers, for 24,844 cases and 45,374 controls. A total of 378 unique biomarkers were identified. Heterogeneity of study design, population type and sample source precluded meta-analysis for all markers except methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). The estimated sensitivity and specificity of mSEPT9 was 80.6% (95% CI 76.6-84.0%) and 88.0% (95% CI 79.1-93.4%) respectively; TuM2-PK had an estimated sensitivity of 81.6% (95% CI 75.2-86.6%) and specificity of 80.1% (95% CI 76.7-83.0%). CONCLUSION Two novel biomarkers (mSEPT9 and TuM2-PK) were identified from the literature with potential for use in lower-prevalence populations. Further research is needed to validate these biomarkers in primary care for screening and assessment of symptomatic patients.
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Affiliation(s)
- Paige Druce
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia.
| | - Natalia Calanzani
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Claudia Snudden
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Kristi Milley
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia
| | - Rachel Boscott
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Dawnya Behiyat
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Javiera Martinez-Gutierrez
- Department of Family Medicine, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Smiji Saji
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Jasmeen Oberoi
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia
| | - Garth Funston
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Mike Messenger
- Leeds Institute of Health Sciences, University of Leeds, Leeds, UK
| | - Fiona M Walter
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Jon Emery
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Melbourne, VIC, Australia
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
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37
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Exosome-mediated diagnosis of pancreatic cancer using lectin-conjugated nanoparticles bound to selective glycans. Biosens Bioelectron 2021; 177:112980. [DOI: 10.1016/j.bios.2021.112980] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 12/31/2020] [Accepted: 01/02/2021] [Indexed: 12/21/2022]
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Du Z, Zhang X, Gao W, Yang J. Differentially expressed genes PCCA, ECHS1, and HADH are potential prognostic biomarkers for gastric cancer. Sci Prog 2021; 104:368504211011344. [PMID: 33881965 PMCID: PMC10358502 DOI: 10.1177/00368504211011344] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Gastric cancer (GC) is one of the most common malignant tumors in the world. As far as we know, no biomarker has been widely accepted for early diagnosis and prognosis prediction of GC. The purpose of this study is to find potential biomarkers to predict the prognosis of GC. The differentially expressed gene (DEG) was analyzed from GSE93774. Enrichr was used to analyze the gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the enrichment of transcription factors (TF), miRNA, and kinase. GO analysis showed DEGs was enriched in the process of amino acid metabolism. Pathway results showed DEGs was mainly enriched in cell cycle. Propionyl CoA carboxylase alpha (PCCA), Enoyl coenzyme A hydratase short chain 1 (ECHS1), and 3-hydroxyacyl-CoA dehydrogenase (HADH) have prognostic value in patients with GC. ECHS1 and HADH genes were significantly associated with disease-free survival. There was a significant correlation between PCCA and overall survival rate. The results of this study suggest that PCCA, ECHS1, and HADH may be new biomarkers for predicting the prognosis of GC.
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Affiliation(s)
- Zhongxiang Du
- Clinical Laboratory, Danyang People’s Hospital of Jiangsu Province, Danyang, Jiangsu, China
| | - Xiajun Zhang
- Clinical Laboratory, Danyang People’s Hospital of Jiangsu Province, Danyang, Jiangsu, China
| | - Weiya Gao
- Clinical Laboratory, Danyang People’s Hospital of Jiangsu Province, Danyang, Jiangsu, China
| | - Jie Yang
- Clinical Laboratory, Danyang People’s Hospital of Jiangsu Province, Danyang, Jiangsu, China
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Calanzani N, Druce PE, Snudden C, Milley KM, Boscott R, Behiyat D, Saji S, Martinez-Gutierrez J, Oberoi J, Funston G, Messenger M, Emery J, Walter FM. Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review. Adv Ther 2021; 38:793-834. [PMID: 33306189 PMCID: PMC7889689 DOI: 10.1007/s12325-020-01571-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 11/11/2020] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations. METHODS We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted on types of biomarkers, populations and outcomes. Heterogeneity prevented pooling of outcomes. RESULTS We identified 149 eligible studies, involving 22,264 cancer cases and 49,474 controls. A total of 431 biomarkers were identified (183 microRNAs and other RNAs, 79 autoantibodies and other immunological markers, 119 other proteins, 36 metabolic markers, 6 circulating tumour DNA and 8 other). Over half (n = 231) were reported in pancreatic cancer studies. Only 35 biomarkers had been investigated in at least two studies, with reported outcomes for that individual marker for the same tumour type. Apolipoproteins (apoAII-AT and apoAII-ATQ), and pepsinogens (PGI and PGII) were the most promising biomarkers for pancreatic and gastric cancer, respectively. CONCLUSION Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended.
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Affiliation(s)
- Natalia Calanzani
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
| | - Paige E Druce
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
| | - Claudia Snudden
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Kristi M Milley
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
| | - Rachel Boscott
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Dawnya Behiyat
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Smiji Saji
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Javiera Martinez-Gutierrez
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
- Department of Family Medicine, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Jasmeen Oberoi
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
| | - Garth Funston
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Mike Messenger
- Leeds Centre for Personalised Medicine and Health, University of Leeds, Leeds, UK
| | - Jon Emery
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
| | - Fiona M Walter
- The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- Centre for Cancer Research and Department of General Practice, University of Melbourne, Victoria, Australia
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40
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Tong Y, Zhao Y, Shan Z, Zhang J. CA724 predicts overall survival in locally advanced gastric cancer patients with neoadjuvant chemotherapy. BMC Cancer 2021; 21:4. [PMID: 33402124 PMCID: PMC7786973 DOI: 10.1186/s12885-020-07666-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 11/19/2020] [Indexed: 02/06/2023] Open
Abstract
Background Serum tumor markers including AFU, AFP, CEA, CA199, CA125 and CA724, are of great importance in the diagnosis, prognostic prediction and recurrence monitoring of gastrointestinal malignancies. However, their significance in gastric cancer (GC) patients with neoadjuvant therapy (NCT) is still uncertain. The aim of this study was to evaluate the predictive value of these six tumor markers in locally advanced GC patients who underwent NCT and curative surgery. Methods In total, 290 locally advanced GC patients who underwent NCT and D2 radical gastrectomy were retrospectively analyzed. Data on their tumor markers before (pre-) and after (post-) NCT and pathological characteristics were extracted from the database of our hospital. The optimal cutoff values of the six tumor markers were calculated by the ROC curve and Youden index. Their predictive significance was analyzed and survival curves for overall survival (OS) were obtained by the Kaplan-Meier method. Associations between categorical variables were explored by the chi-square test or Fisher’s exact test. Multivariate analyses were performed by the Cox regression model. Results Pre- and post-CA199, −CA125 and -CA724 could predict overall survival (all P < 0.05), but only the change (diff-) of CA199 was related to prognosis (P = 0.05). In the multivariable analysis, pre- (P = 0.014) and post-CA724 (P = 0.036) remained significant, though diff-CA724 was not an independent prognostic factor (P = 0.581). In addition, pre- and post-CA199, −CA125 and -CA724 were associated with lymph node metastasis (N- vs N+) and pathological stage (I-II vs III) (all P < 0.05). Moreover, post-CA724 was related to the vascular or lymphatic invasion (P = 0.019), while pre-CA724 was not (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05). Conclusions CA724 is an independent factor for prognosis and could be used to predict ypN and ypTNM stage in locally advanced GC patients undergoing NCT and curative resection.
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Affiliation(s)
- Yilin Tong
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, No 44 of Xiaoheyan Road, Dadong District, Liaoning, 110042, Shenyang, China
| | - Yan Zhao
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, No 44 of Xiaoheyan Road, Dadong District, Liaoning, 110042, Shenyang, China
| | - Zexing Shan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, No 44 of Xiaoheyan Road, Dadong District, Liaoning, 110042, Shenyang, China
| | - Jianjun Zhang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, No 44 of Xiaoheyan Road, Dadong District, Liaoning, 110042, Shenyang, China.
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41
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Qader G, Aali M, Smail SW, Mahmood K, Hasan B, M-Amen K, Rahman DB, Qadir FA, Mohammad DK, Najmuldeen HH, Rahman FM, Ahmad SI, Salih NS, Khdhr ZM, Mohammed BA, Majeed AM, Hasan XM, Khidhir BH, Muhammad ES, Muhamadsalih BA, Hasan SK, Hamad AJ, Esmail ZK, Ismael CM, Husaen SM, Abdulla CA, Hussen BM, Housein Z, Shekha M, Salihi A. Cardiac, Hepatic and Renal Dysfunction and IL-18 Polymorphism in Breast, Colorectal, and Prostate Cancer Patients. Asian Pac J Cancer Prev 2021; 22:131-137. [PMID: 33507690 PMCID: PMC8184168 DOI: 10.31557/apjcp.2021.22.1.131] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION The present study aimed to determine the alterations in the serum levels of tumor markers used to evaluate cardiac, renal and liver function, and detect the interleukin (IL)-18 rs1946518 polymorphism in breast (BC), colorectal (CRC) and prostate cancer (PCa) patients. METHODS Blood samples were collected from 65 female BC, 116 CRC, 79 PCa and 88 myocardial infarction (MI) patients, and 110 healthy individuals to determine the concentration of tumor and cardiac markers. Furthermore, the IL-18 rs1946518 polymorphism was assessed using amplification refractory mutation system (ARMS)-PCR. RESULTS The serum levels of the tumor markers cancer antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and total prostate-specific antigen (TPSA) were significantly increased in cancer patients compared with healthy controls. Furthermore, the activity of high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase‑myocardial band (CK-MB) was enhanced in MI patients, however, their activity was unchanged in cancer patients. The activity of alkaline phosphatase (ALP), and the serum concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea were markedly elevated in CRC and PCa patients, respectively, compared with the control group. Although, no significant differences were observed in the -607 C/A polymorphism and allele frequency of IL-18 among BC, CRC patients and healthy individuals, the odds ratio (OR) was 1.75 for both C and A allele in BC patients. Therefore, the -607 C/A polymorphism could be considered as a risk factor for BC. CONCLUSION The aforementioned results suggested that tumor markers could be considered as excellent biomarkers for the early detection of BC, CRC and PCa, whereas the concentration of liver enzymes could serve as an alternative indicator for the diagnosis of CRC and PCa. Additionally, the rs1946518 polymorphism in the IL-18 gene could be considered as a risk factor for the occurrence of BC, CRC and PCa.<br />.
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Affiliation(s)
- Govand Qader
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Mukhlis Aali
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Shukur W Smail
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq.,Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq
| | - Kazhan Mahmood
- Department of Midwifery, College of Nursing, Hawler Medical University, Erbil, Kurdistan Region, Iraq
| | - Bestoon Hasan
- Department of Cancer Registry, Cancer Control Unit, Erbil Directorate of Health, Erbil, Iraq
| | - Karwan M-Amen
- Department of Medical Analysis, Faculty of Science, Tishk International University, Erbil, Iraq.,Department of Nursing, College of Nursing, Hawler Medical University, Erbil, Kurdistan Region, Iraq
| | - Dlzar Bayz Rahman
- Internal Laboratory, Hawler Teaching Hospital, Erbil Directorate of Health, Erbil, Iraq
| | - Fikry A Qadir
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Dara K Mohammad
- College of Agricultural Engineering Sciences, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq.,Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, 141 83 Stockholm, Sweden
| | - Hastyar H Najmuldeen
- Department of Biology, College of Science, University of Sulaimani, Kurdistan Region, Iraq.,Medical Laboratory Analysis, Cihan University-Sulaimaniya, Slemani, Iraq
| | - Fryad Majeed Rahman
- Department of Biology, College of Science, University of Sulaimani, Kurdistan Region, Iraq
| | - Seepal Ibrahim Ahmad
- Emergency Hospital, Duhok General Health Directorate, Duhok, Kurdistan Region, Iraq
| | - Nergz S Salih
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Zainab M Khdhr
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Bushra A Mohammed
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Asuda M Majeed
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Xanda M Hasan
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Bushra H Khidhir
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Eman S Muhammad
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Bahar A Muhamadsalih
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Simav K Hasan
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Aram J Hamad
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Zahra K Esmail
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Chra M Ismael
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Shan M Husaen
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Chiavan A Abdulla
- Department of Pathological Analysis, Faculty of Science, University of Knowledge, Erbil, Kurdistan Region, Iraq
| | - Bashdar M Hussen
- College of Pharmacy, Hawler Medical University, Kurdistan Region, Iraq
| | - Zjwan Housein
- Department of Medical Laboratory Technology, Health Technical College, Erbil Polytechnic University, Erbil, Iraq
| | - Mudhir Shekha
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
| | - Abbas Salihi
- Department of Biology, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq.,Department of Nursing, College of Nursing, Hawler Medical University, Erbil, Kurdistan Region, Iraq
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42
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Jing R, Liu S, Jiang Y, Zong W, Ju S, Cui M. Determination of serum RP11-731F5.2 as a noninvasive biomarker for gastric cancer diagnosis and prognosis. Pathol Res Pract 2020; 216:153261. [DOI: 10.1016/j.prp.2020.153261] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 10/16/2020] [Accepted: 10/17/2020] [Indexed: 12/12/2022]
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Bitter EE, Townsend MH, Erickson R, Allen C, O'Neill KL. Thymidine kinase 1 through the ages: a comprehensive review. Cell Biosci 2020; 10:138. [PMID: 33292474 PMCID: PMC7694900 DOI: 10.1186/s13578-020-00493-1] [Citation(s) in RCA: 75] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 11/09/2020] [Indexed: 12/23/2022] Open
Abstract
Proliferation markers, such as proliferating cell nuclear antigen (PCNA), Ki-67, and thymidine kinase 1 (TK1), have potential as diagnostic tools and as prognostic factors in assessing cancer treatment and disease progression. TK1 is involved in cellular proliferation through the recovery of the nucleotide thymidine in the DNA salvage pathway. TK1 upregulation has been found to be an early event in cancer development. In addition, serum levels of TK1 have been shown to be tied to cancer stage, so that higher levels of TK1 indicate a more serious prognosis. As a result of these findings and others, TK1 is not only a potentially viable biomarker for cancer recurrence, treatment monitoring, and survival, but is potentially more advantageous than current biomarkers. Compared to other proliferation markers, TK1 levels during S phase more accurately determine the rate of DNA synthesis in actively dividing tumors. Several reviews of TK1 elaborate on various assays that have been developed to measure levels in the serum of cancer patients in clinical settings. In this review, we include a brief history of important TK1 discoveries and findings, a comprehensive overview of TK1 regulation at DNA to protein levels, and recent findings that indicate TK1’s potential role in cancer pathogenesis and its growing potential as a tumor biomarker and therapeutic target.
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Affiliation(s)
- Eliza E Bitter
- Department of Microbiology and Molecular Biology, Brigham Young University, 701 E University Pkwy, LSB room 4007, Provo, UT, 84602, USA.
| | - Michelle H Townsend
- Department of Microbiology and Molecular Biology, Brigham Young University, 701 E University Pkwy, LSB room 4007, Provo, UT, 84602, USA
| | - Rachel Erickson
- Department of Microbiology and Molecular Biology, Brigham Young University, 701 E University Pkwy, LSB room 4007, Provo, UT, 84602, USA
| | - Carolyn Allen
- Department of Microbiology and Molecular Biology, Brigham Young University, 701 E University Pkwy, LSB room 4007, Provo, UT, 84602, USA
| | - Kim L O'Neill
- Department of Microbiology and Molecular Biology, Brigham Young University, 701 E University Pkwy, LSB room 4007, Provo, UT, 84602, USA.
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Singh S, Kumar R, Kumar U, Kumari R. Clinical Significance and Role of TK1, CEA, CA 19-9 and CA 72-4 levels in Diagnosis of Colorectal Cancers. ASIAN PACIFIC JOURNAL OF CANCER PREVENTION : APJCP 2020; 21:3133-3136. [PMID: 33247667 PMCID: PMC8033132 DOI: 10.31557/apjcp.2020.21.11.3133] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Indexed: 01/10/2023]
Abstract
To explore the diagnostic value, pre-operative serum thymidine kinase 1(TK1), CEA, CA 19-9 and CA 72-4 levels were measured in 106 patients with colorectal carcinoma (53 colon and 53 rectal carcinoma patients) and 53 healthy controls. Sandwich Elisa, biotin-labeled antibody kit was used for TK1, and other tumor markers were measured using electro-chemiluminescence. Serum TK1 levels were significantly higher in CRC than in healthy controls (p<0.05) and showed significant associations with tumor stage, histopathological grade, lymph node status and metastasis (p<0.01). TK1 showed the highest (0.824-0.862) area under receiver operating characteristics curve (AUC) in comparison to other markers, and the AUC of the panel of combination tests performed even better (0.935-0.952). Significant variation was observed between the single biomarker test and their combination (Z test, p<0.01) and the Hosmer-Lemeshow test showed an adequate model of calibration. The algorithm based on combination of TK1, CEA, CA19-9 and CA72-4 can improve the diagnostic efficiency in CRC patients.
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Affiliation(s)
- Swarnima Singh
- Department of Biochemistry, Netaji Subhas Medical College and Hospital, Patna, India
| | - Rakesh Kumar
- Department of Surgical Gastroenterology and Liver Transplant, Indira Gandhi Institute of Medical Sciences, Patna, India
| | - Uday Kumar
- Department of Biochemistry, Netaji Subhas Medical College and Hospital, Patna, India
| | - Rekha Kumari
- Department of Biochemistry, Indira Gandhi Institute of Medical Sciences, Patna, India
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Ma W, Li W, Wang J, Wu R, Liu C, Feng F, Jiang X. The Clinical Role of Preoperative Serum CA19-9 and Carcinoembryonic Antigen (CEA) Levels in Evaluating the Resectability of Advanced Gallbladder Cancer. Med Sci Monit 2020; 26:e925017. [PMID: 32950997 PMCID: PMC7513615 DOI: 10.12659/msm.925017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The present study was designed to study the ability of preoperative serum concentrations of the tumor-associated biomarkers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and adjusted CA19-9 to assess the resectability of advanced gallbladder cancer (GBC). MATERIAL AND METHODS This retrospective study included patients with potentially resectable stage II-IV (AJCC 8th) GBC examined at our institution between January 2012 and December 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive value and optimal cut-off point of tumor-associated biomarkers for curative resection. RESULTS Pathological examination of the 309 patients included in this study found that 169 (54.7%) underwent R0 (curative) resection, whereas 121 (39.2%) underwent R1/2 (non-curative) resection, and 19 (6.1%) were unresectable. The mean serum concentrations of CEA, CA19-9 and adjusted CA19-9 were significantly lower in patients who underwent R0 resection than in the other groups. ROC curve analysis showed that adjusted CA19-9 concentration was better able to predict resectability (area under the curve, 0.774; 95% confidence interval, 0.722-0.826; P<0.001) than total bilirubin, CEA, and CA19-9 concentrations. The optimal cut-off for adjusted CA19-9 concentration was 47.63 U/mL, which had a sensitivity of 69.82%, a specificity of 75%, a positive predictive value of 77.12% and a negative predictive value of 67.31%. CONCLUSIONS Adjusted CA19-9 concentration is an easily calculated parameter superior to CA19-9 and CEA concentrations in predicting the resectability of advanced gallbladder cancer.
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Affiliation(s)
- Wencong Ma
- Department of Biliary Tract Surgery I, Third Affiliated Hospital of Second Military Medical University, Shanghai, China (mainland)
| | - Wei Li
- Department of Biliary Tract Surgery I, Third Affiliated Hospital of Second Military Medical University, Shanghai, China (mainland)
| | - Jinghan Wang
- Department of Biliary Tract Surgery I, Third Affiliated Hospital of Second Military Medical University, Shanghai, China (mainland)
| | - Rui Wu
- Department of Biliary Tract Surgery I, Third Affiliated Hospital of Second Military Medical University, Shanghai, China (mainland)
| | - Chen Liu
- Department of Biliary Tract Surgery I, Third Affiliated Hospital of Second Military Medical University, Shanghai, China (mainland)
| | - Feiling Feng
- Department of Biliary Tract Surgery I, Third Affiliated Hospital of Second Military Medical University, Shanghai, China (mainland)
| | - Xiaoqing Jiang
- Department of Biliary Tract Surgery I, Third Affiliated Hospital of Second Military Medical University, Shanghai, China (mainland)
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46
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Chen YY, Feng Y, Mao QS, Ma P, Liu JZ, Lu W, Liu YF, Chen X, Hu YL, Xue WJ. Diagnostic and prognostic value of the peripheral natural killer cell levels in gastric cancer. Exp Ther Med 2020; 20:3816-3822. [PMID: 32855731 PMCID: PMC7444348 DOI: 10.3892/etm.2020.9101] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 06/24/2020] [Indexed: 12/13/2022] Open
Abstract
Peripheral blood lymphocyte subsets have been reported to be useful as prognostic and/or diagnostic markers for patients with cancer. However, the clinical value of peripheral blood lymphocyte subsets in gastric cancer (GC) has remained elusive. In the present study, peripheral CD3+, CD4+ and CD8+ T lymphocytes, B cells (CD19+), regulatory T cells (Tregs; CD4+CD25+CD127-) and natural killer (NK) cells (CD3-CDl6+CD56+) were detected by flow cytometry in 122 patients with GC, 80 healthy donors (HDs) and 80 patients with gastric ulcer (GU). NK cells (CD56+) were detected by immunohistochemical (IHC) analysis in 20 GC and three GU tissue samples. A receiver-operating characteristic (ROC) curve was used to determine the threshold of the peripheral NK cell level and survival analysis was performed to assess its prognostic value in patients with GC. The results indicated that the peripheral NK cell proportion in patients with GC (18.77%) was significantly higher than that in the HD (12.19%) and GU (12.74%) groups. IHC analysis suggested that the NK level in GC tumor samples was correlated with that in paired serum samples. ROC curve analysis indicated that the peripheral NK cell level (15.16%) was able to effectively identify patients with GC, a diagnostic sensitivity of 75.41% and a specificity of 77.45% were determined. Multivariate logistic regression analysis revealed that the peripheral NK cell level was independently associated with the T stage and survival analysis demonstrated that high levels of peripheral NK cells were associated with poor prognosis of patients with GC. In conclusion, the peripheral NK cell level may be a diagnostic and prognostic marker for patients with GC.
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Affiliation(s)
- Yu-Yan Chen
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.,Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Ying Feng
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Qin-Sheng Mao
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Peng Ma
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Jia-Zhou Liu
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.,Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Wei Lu
- Department of Hematology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Yi-Fei Liu
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Xi Chen
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Yi-Lin Hu
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.,Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Wan-Jiang Xue
- Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.,Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
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Expression of Pregnancy Specific β-1 Glycoprotein 1 in Cervical Cancer Cells. Arch Med Res 2020; 51:504-514. [PMID: 32546445 DOI: 10.1016/j.arcmed.2020.05.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 04/25/2020] [Accepted: 05/07/2020] [Indexed: 11/24/2022]
Abstract
BACKGROUND Cervical Cancer (CC) is a worldwide public health concern associated with genetic alterations, among these the gain of the 19q chromosome harboring the Pregnancy Specific Glycoproteins (PSG) gene family. These proteins play a critical role in pregnancy, with participation in immunotolerance, angiogenesis, and invasion processes, which are also observed in carcinogenesis. The aim of this study was to determine the molecular alterations of PSG1 and its relationship with CC. METHODS PSG1 Copy Number Variation (CNV) was evaluated in 31 CC and eight normal cervical tissues by qPCR. PSG1 expression was correlated with HPV detection and IL-10 and TGF-β expression in CC samples. Finally, PSG1 protein expression was evaluated by immunofluorescence in CC cell lines, by immunohistochemistry in a tissue microarray, and by immunoblotting in the sera of women with normal cervix, pre-invasive lesions, and CC. RESULTS PSG1 showed a gain of 25.6% in CNV and gene expression in CC. There was a lack of PSG1 expression in normal cervical epithelium and positive immunostaining in 57% of CC tissues, while all CC cell lines expressed PSG1. Finally, PSG1 was immunodetected in 90% of pre-invasive lesions and in all CC serum samples, but not in healthy women. PSG1 expression correlates with the expression of IL-10 and TGF-β in CC tissues, but not with the presence of HPV. CONCLUSION These data show evidence of the differential expression of PSG1 in CC that could explain its participation in tumor-biology and immunotolerance mechanisms. Further, its immunodetection could provide early detection of this cancer.
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Luo H, Shen K, Li B, Li R, Wang Z, Xie Z. Clinical significance and diagnostic value of serum NSE, CEA, CA19-9, CA125 and CA242 levels in colorectal cancer. Oncol Lett 2020; 20:742-750. [PMID: 32566000 PMCID: PMC7286116 DOI: 10.3892/ol.2020.11633] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 01/17/2020] [Indexed: 01/23/2023] Open
Abstract
The present study investigated the value of combinations of five specific tumor biomarkers for the diagnosis of colorectal cancer (CRC): Neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cancer antigen (CA)19-9, CA125 and CA242. Associations between these markers and clinicopathological characteristics (including the Tumor-Node-Metastasis stage) were also assessed. Serum levels of the 5 markers were compared between 358 patients with CRC and 298 healthy individuals (CRC and control group, respectively). The NSE concentration of the CRC group was significantly higher compared with the control. Furthermore, patients at clinical stage III+IV exhibited significantly higher NSE levels compared with those at stage I+II. The serum NSE level of N+ patients was significantly higher compared with the N− group, and the NSE level of M1 patients was significantly compared with the M0 group. NSE level was also significantly associated with tumor stage, lymph node metastasis, distant metastasis and hematochezia. The area under the receiver operating characteristic curve (AUC) for NSE in CRC was 0.766, which was significantly higher than that of the other four markers, which ranged from 0.560–0.682. The AUC of NSE, CEA, CA19-9, CA125, CA242 combined was significantly higher compared with any of the markers individually (range, 0.796–0.858). Therefore, serum NSE may be a good clinical tool for the auxiliary diagnosis of colorectal cancer. Besides, the combination of NSE, CEA, CA19-9, CA125 and CA242 was significantly more sensitive compared with NSE alone. Thus, the combined detection of the 5 tumor markers may be more useful for the diagnosis of CRC.
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Affiliation(s)
- Hai Luo
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
| | - Kexin Shen
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
| | - Bo Li
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
| | - Ruiqi Li
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
| | - Zeming Wang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
| | - Zhongshi Xie
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
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Chen W, Liang JL, Zhou K, Zeng QL, Ye JW, Huang MJ. Effect of CIP2A and its mechanism of action in the malignant biological behavior of colorectal cancer. Cell Commun Signal 2020; 18:67. [PMID: 32321509 PMCID: PMC7178757 DOI: 10.1186/s12964-020-00545-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 03/06/2020] [Indexed: 02/07/2023] Open
Abstract
Background Increasing evidence has revealed a close correlation between cancerous inhibitor of protein phosphatase 2A (CIP2A) and cancer progression. CIP2A has been shown to participate in diverse biological processes, such as development, tumorigenic transformation and chemoresistance. However, the functions of CIP2A in colorectal cancer (CRC) and its underlying mechanisms of action are not yet completely understood. The purpose of this study was to explore its clinical significance, function and relevant pathways in CRC. Methods Quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC), western blotting and enzyme-linked immunosorbent assay (ELISA) were used to identify the expression of CIP2A in CRC tissues, sera and CRC cell lines. The association between the expressions of CIP2A and patient survival was analyzed using the Kaplan-Meier curves. Additionally, the functional role of CIP2A in the cell lines was identified through small interfering RNA (siRNA)-mediated depletion of the protein followed by analyses of proliferation and xenograft growth in vivo using short hairpin (sh) RNAs. Effects of the C-myc inhibitor 10,058-F4 on the expressions of C-myc, and CIP2A in CRC cell lines and its potential mechanisms of action were investigated. Finally, the potential molecular pathways associated with CIP2A were screened using the phosphokinase array and identified through western blotting. Results CIP2A mRNA and protein levels were upregulated in CRC tissues compared to those of the corresponding normal tissues. It can be used as an independent prognostic indicator to determine overall survival (OS) and disease-free survival (DFS). Depletion of CIP2A substantially suppressed the growth of CRC cells and colony formation in vitro, and inhibited the growth of xenograft tumors in vivo. Additionally, the levels of CIP2A in the sera of patients with CRC were higher than those of the control subjects. Multivariate analyses revealed that the levels of CIP2A in the sera were not independent prognostic indicators in patients with CRC. Moreover, 10,058-F4 could effectively inhibit the growth of CRC cells in vitro, which could be correlated with an inhibition in the expressions of C-myc, CIP2A and its downstream regulatory anti-apoptotic proteins. Furthermore, the Human Phosphokinase Antibody Array was used to gain insights into the CIP2A-dependent intermediary signaling pathways. The results revealed that several signaling pathways were affected and the protein levels of p-p53 (S392), p-STAT5a (Y694), Cyclin D1, p-ERK1/2 and p-AKT (T308) had decreased in CIP2A-shRNA group based on the results of the western blot analysis. Conclusions CIP2A could promote the development of CRC cells and predict poor prognosis in patients with CRC, suggesting that it may serve as a potential prognostic marker and therapeutic target against CRC.
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