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Yang HC, Fu CF, Qiao LJ, Long GH, Yang LF, Yao B. Relationship between Helicobacter pylori infection and programmed death-ligand 1 in gastric cancer: A meta-analysis. World J Clin Oncol 2025; 16:102397. [DOI: 10.5306/wjco.v16.i4.102397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/04/2024] [Accepted: 02/06/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) is one of the most common malignancies worldwide, and Helicobacter pylori (HP) infection is a well-established risk factor for its development. Programmed death-ligand 1 (PD-L1) expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment. While HP infection and PD-L1 expression in GC may be linked, the relationship between them remains unclear, in part because there have been conflicting results reported from various studies.
AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.
METHODS A systematic literature review was conducted using PubMed, Embase, Cochrane Library, and Web of Science databases. Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included. Odds ratios and 95% confidence intervals were calculated to estimate the association. Heterogeneity was assessed using Cochrane’s Q test and I² statistic. A random-effects model was used due to significant heterogeneity across studies.
RESULTS Fourteen studies involving a total of 3069 patients with GC were included. The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues (odd ratio = 1.69, 95% confidence interval: 1.24-2.29, P < 0.001, I2 = 59%). Sensitivity analyses confirmed the robustness of these findings. Subgroup analyses did not show significant variation based on geographic region, sample size, or method of PD-L1 assessment. Publication bias was minimal, as shown by funnel plots and Egger’s regression test.
CONCLUSION HP infection is associated with increased PD-L1 expression in GC, suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.
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Affiliation(s)
- Hong-Chang Yang
- Department of Gastroenterology, Longgang Central Hospital of Shenzhen, Shenzhen 518100, Guangdong Province, China
| | - Cheng-Feng Fu
- Department of Oncology, Tongren People’s Hospital, Tongren 554300, Guizhou Province, China
| | - Li-Jun Qiao
- Department of Basic Medical Sciences, Guizhou Health Vocational College, Tongren 554300, Guizhou Province, China
| | - Gen-He Long
- Department of School of Medicine, Guizhou Vocational and Technical College, Tongren 554300, Guizhou Province, China
| | - Li-Fen Yang
- Department of Oncology, Tongren People’s Hospital, Tongren 554300, Guizhou Province, China
| | - Biao Yao
- Department of Oncology, Tongren People’s Hospital, Tongren 554300, Guizhou Province, China
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Li Y, Piao Z, Ge X, Feng J, Sun D, Zhang J. Environmental pollutants and rectal cancer: The impact of water contamination. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 294:118072. [PMID: 40127547 DOI: 10.1016/j.ecoenv.2025.118072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 03/14/2025] [Accepted: 03/14/2025] [Indexed: 03/26/2025]
Abstract
BACKGROUND Water is a fundamental resource for life, and exposure to water contamination has far-reaching implications for an increased risk of tumor diseases. METHODS Studies of rectal and colorectal cancer related to water contamination were identified from the published literature in the PUBMED databases from 2010 to 2024. RESULTS This review provides a critical analysis of the current evidence, summarizing the association of water contamination, including industrial waste, pesticides, heavy metals, with rectal and colorectal cancer. It highlights their impact on rectal and colorectal cancer progression by underlying processes of DNA damage, chronic inflammation, and microbial contamination. CONCLUSION Rectal cancer is a significant global health concern with a strong association between environmental pollutants in water sources and increased incidence of rectal cancer. It is vital to identify how waster pollutants influence the development and progression of rectal cancer and formulate targeted preventive approaches and social interventions to decrease the disease's impact.
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Affiliation(s)
- Yezhou Li
- Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Zhe Piao
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xinbin Ge
- Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Jinbao Feng
- Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Denghua Sun
- Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
| | - Jiayu Zhang
- Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
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He QC, Huang ZN, Lv CB, Wu YH, Qiu WW, Ma YB, Wu J, Zheng CY, Lin GS, Li P, Wang JB, Lin JX, Lin M, Tu RH, Zheng CH, Huang CM, Cao LL, Xie JW. Effect of Helicobacter pylori infection on survival outcomes of patients undergoing radical gastrectomy after neoadjuvant chemotherapy: a multicenter study in China. BMC Cancer 2025; 25:460. [PMID: 40082850 PMCID: PMC11907980 DOI: 10.1186/s12885-025-13840-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 02/28/2025] [Indexed: 03/16/2025] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) has been confirmed to improve the prognosis of patients with advanced gastric cancer (AGC). However, no study has investigated whether Helicobacter pylori (HP) infection affects the postoperative survival of patients who receive NAC. METHODS This retrospective cohort study included 307 patients with AGC who underwent laparoscopic radical gastrectomy after NAC at three hospitals in China between January 1, 2016, and April 31, 2020. Cox regression was used to assess prognostic factors for survival. Kaplan-Meier was used for survival analysis. RESULTS The HP + and the HP- group included 141 and 166 cases. The 3-year overall survival (OS) and disease-free survival (DFS) of the HP + group were significantly better than the HP- group (3-year OS: 75.9% vs. 60.2%, 3-year DFS: 70.2% vs. 52.3%; All P < 0.001). For the HP + group, ypTNM Stage III (HR, 4.00; 95% CI, 1.11-14.39; P = 0.034), NAC ≥ 4 cycles (HR, 0.43; 95% CI, 0.20-0.90; P = 0.026), and adjuvant chemotherapy (AC) ≥ 4 cycles (HR, 0.20; 95% CI, 0.09-0.48; P < 0.001) are independent prognostic factors for OS. In the cohort of HP + patients who received ≥ 4 cycles of NAC, the prognosis of patients who received ≥ 4 cycles of AC after surgery was better than that of patients who received < 4 cycles of AC (3-year OS: 92.5% vs 71.4%; P = 0.042). CONCLUSIONS Following NAC, HP + patients with AGC exhibit better prognosis than that of HP- counterparts. For potentially resectable HP + AGC patients, radical surgery following ≥ 4 cycles of NAC with ≥ 4 cycles of sequential AC might be recommended to improve survival.
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Affiliation(s)
- Qi-Chen He
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Chen-Bin Lv
- Department of Gastrointestinal Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
| | - Yong-He Wu
- Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University, ZhangZhou, China
| | - Wen-Wu Qiu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Yu-Bin Ma
- Department of Gastrointestinal Surgery, Qinghai University Affiliated Hospital, Xining, China
| | - Ju Wu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
- Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Chang-Yue Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Putian University, Putian, China
| | - Guo-Sheng Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, No. 29 Xinquan Rd, Fuzhou, 350001, Fujian Province, China.
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.
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Herdan RA, Taher MG, Shafiq AM, Omran OM, Abozaid L, Babiker N, AlQahtani SA, Taha NM, Taha NM, Shubaili AAY, Khubrani SAA, Ameen MG. Evaluation of the relationship between H. Pylori-infected gastric mucosa and prognosis of gastrointestinal stromal tumor. Int J Health Sci (Qassim) 2025; 19:41-48. [PMID: 39760053 PMCID: PMC11699233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025] Open
Abstract
Objective Gastrointestinal stromal tumor (GIST) is the most common type of mesenchymal tumor accounting for 2.2% of all malignant gastric tumors. Mesenchymal stem cells (MSCs) play crucial roles in gastric carcinogenesis. In addition, Helicobacter pylori has been linked to GIST as it induces an epithelial response that can home MSCs to the stomach mucosa. This study aimed to investigate the relationship between H. pylori-infected gastric mucosa and the development of CD117-positive GIST and evaluate the prognosis of H. pylori-infected gastric mucosa of GIST patients that received anti-CD117 therapy. Methods This is a retrospective study conducted on H. pylori-infected GIST patients diagnosed between 2015 and 2021. The follow-up period was performed for a minimum of 2 years. Clinicopathological factors for each patient were collected from cases selected from the Registry of Pathology and Surgery Departments at Assiut University Hospitals. Results There was a statistically significant difference between our study population regarding the overall survival of studied patients, disease-free survival of studied patients, and the relationship between H. pylori-infected gastric mucosa and development, grading, therapy response, and overall survival of GIST except in status at last follow-up. Conclusions Our study is the first to reveal that H. pylori infection is linked to a worse prognosis for GIST patients. H. pylori has the potential to be used as a strong predictive biomarker for GIST individuals in the future. Clinical research with large samples as well as prospective designs are needed to confirm this connection.
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Affiliation(s)
- Rania A. Herdan
- Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Mohamed Gamal Taher
- Department of General Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ahmed Mahran Shafiq
- Department of Medical Oncology and Hematological Malignancies, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
| | - Ola M. Omran
- Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
- Department of Pathology, College of Medicine, Qassim University, Buridah, Qassim Region, Saudi Arabia
| | - Lobaina Abozaid
- Department of Pathology, College of Medicine, Qassim University, Buridah, Qassim Region, Saudi Arabia
| | - Nahla Babiker
- Department of Pathology, College of Medicine, Qassim University, Buridah, Qassim Region, Saudi Arabia
| | - Saeed A. AlQahtani
- Department of Clinical Practice, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
| | - Nada M. Taha
- Medical Student, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Noha M. Taha
- Medical Student, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Aisha Ahmed Y. Shubaili
- Department of Medical laboratory King Khalid University Medical city, Abha 62223, Saudi Arabia
| | | | - Mahmoud Gamal Ameen
- Department of Oncologic Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt
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Luan X, Zhao L, Zhang F, Wang W, Jiao F, Zhou X, Niu P, Han X, Zhang X, Zhao D, He M, Guan Q, Li Y, Chen Y. Sex disparity, prediagnosis lifestyle factors, and long-term survival of gastric cancer: a multi-center cohort study from China. BMC Cancer 2024; 24:1149. [PMID: 39285317 PMCID: PMC11403820 DOI: 10.1186/s12885-024-12873-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 08/29/2024] [Indexed: 09/20/2024] Open
Abstract
BACKGROUND This multi-center cohort study aimed to investigate whether sex and prediagnosis lifestyle affect the prognosis of gastric cancer. METHODS Patients with gastric cancer were from four gastric cancer cohorts of the National Cancer Center of China, The First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Provincial Cancer Hospital. Prediagnosis lifestyle factors in our study included body mass index (BMI) at diagnosis, usual BMI, weight loss, the history of Helicobacter pylori (Hp) infection, and the status of smoking and drinking. RESULTS Four gastric cancer cohorts with 29,779 gastric cancer patients were included. In total patients, female patients had a better prognosis than male patients (HR = 0.938, 95%CI: 0.881-0.999, P = 0.046). For prediagnosis lifestyle factors, BMI at diagnosis, usual BMI and the amount of smoking were statistically associated with the prognosis of gastric cancer patients. Female patients with smoking history had a poorer survival than non-smoking females (HR = 0.782, 95%CI: 0.616-0.993, P = 0.044). Tobacco consumption > 40 cigarettes per day (HR = 1.182, 95%CI: 1.035-1.350, P = 0.013) was independent adverse prognostic factors in male patients. Obesity paradox was observed only in male patients (BMI < 18.5, HR = 1.145, 95%CI: 1.019-1.286, P = 0.023; BMI: 23-27.4, HR = 0.875, 95%CI: 0.824-0.930, P < 0.001; BMI ≥ 27.5, HR = 0.807, 95%CI: 0.735-0.886, P < 0.001). CONCLUSIONS Sex and some prediagnosis lifestyle factors, including BMI at diagnosis, usual BMI and the amount of smoking, were associated with the prognosis of gastric cancer.
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Affiliation(s)
- Xiaoyi Luan
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Lulu Zhao
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Fan Zhang
- Lanzhou University Second Hospital, Lanzhou, China
| | - Wanqing Wang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Fuzhi Jiao
- The First Hospital of Lanzhou University, Lanzhou, China
| | - Xiadong Zhou
- Gansu Provincial Cancer Hospital, Lanzhou, China
| | - Penghui Niu
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Xue Han
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Xiaojie Zhang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China
- Gastrointestinal Surgery Department, China-Japan Friendship Hospital, Beijing, China
| | - Dongbing Zhao
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China.
| | - Mingyan He
- Gansu Provincial Cancer Hospital, Lanzhou, China.
| | - Quanlin Guan
- The First Hospital of Lanzhou University, Lanzhou, China.
| | - Yumin Li
- Lanzhou University Second Hospital, Lanzhou, China.
| | - Yingtai Chen
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Beijing, 100021, China.
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Zhang L, Yu F, Zhang Y, Li P. Implications of lncRNAs in Helicobacter pylori-associated gastrointestinal cancers: underlying mechanisms and future perspectives. Front Cell Infect Microbiol 2024; 14:1392129. [PMID: 39035354 PMCID: PMC11257847 DOI: 10.3389/fcimb.2024.1392129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 06/19/2024] [Indexed: 07/23/2024] Open
Abstract
Helicobacter pylori (H. pylori) is a harmful bacterium that is difficult to conveniently diagnose and effectively eradicate. Chronic H. pylori infection increases the risk of gastrointestinal diseases, even cancers. Despite the known findings, more underlying mechanisms are to be deeply explored to facilitate the development of novel prevention and treatment strategies of H. pylori infection. Long noncoding RNAs (lncRNAs) are RNAs with more than 200 nucleotides. They may be implicated in cell proliferation, inflammation and many other signaling pathways of gastrointestinal cancer progression. The dynamic expression of lncRNAs indicates their potential to be diagnostic or prognostic biomarkers. In this paper, we comprehensively summarize the processes of H. pylori infection and the treatment methods, review the known findings of lncRNA classification and functional mechanisms, elucidate the roles of lncRNAs in H. pylori-related gastrointestinal cancer, and discuss the clinical perspectives of lncRNAs.
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Affiliation(s)
- Lei Zhang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
| | | | | | - Peifeng Li
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China
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Mostaghimi T, Bahadoran E, Bakht M, Taheri S, Sadeghi H, Babaei A. Role of lncRNAs in Helicobacter pylori and Epstein-Barr virus associated gastric cancers. Life Sci 2024; 336:122316. [PMID: 38035995 DOI: 10.1016/j.lfs.2023.122316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 11/17/2023] [Accepted: 11/27/2023] [Indexed: 12/02/2023]
Abstract
Helicobacter pylori infection is a risk factor for the development of gastric cancer (GC), and the role of co-infection with viruses, such as Epstein-Barr virus, in carcinogenesis cannot be ignored. Furthermore, it is now known that genetic factors such as long non-coding RNAs (lncRNAs) are involved in many diseases, including GC. On the other side, they can also be used as therapeutic goals. Modified lncRNAs can cause aberrant expression of genes encoding proximal proteins, which are essential for the development of carcinoma. In this review, we present the most recent studies on lncRNAs in GC, concentrating on their roles in H. pylori and EBV infections, and discuss some of the molecular mechanisms of these GC-related pathogens. There was also a discussion of the research gaps and future perspectives.
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Affiliation(s)
- Talieh Mostaghimi
- Department of Medical Microbiology and Biotechnology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Ensiyeh Bahadoran
- School of Medicine, Qazvin University of Medical Science, Qazvin, Iran
| | - Mehdi Bakht
- Medical Microbiology Research Center, Qazvin University of Medical Science, Qazvin, Iran
| | - Shiva Taheri
- Medical Microbiology Research Center, Qazvin University of Medical Science, Qazvin, Iran
| | - Hamid Sadeghi
- Medical Microbiology Research Center, Qazvin University of Medical Science, Qazvin, Iran
| | - Abouzar Babaei
- Medical Microbiology Research Center, Qazvin University of Medical Science, Qazvin, Iran.
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Xiong M, Mohammed Aljaberi HS, Khalid Ansari N, Sun Y, Yin S, Nasifu L, Sun H, Xu T, Pan Y, Nie Z, Liu C, Zhang Z, Jiang Z, Wang S, He B. Phenotype and genotype analysis for Helicobacter pylori antibiotic resistance in outpatients: a retrospective study. Microbiol Spectr 2023; 11:e0055023. [PMID: 37732751 PMCID: PMC10580949 DOI: 10.1128/spectrum.00550-23] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 07/06/2023] [Indexed: 09/22/2023] Open
Abstract
To investigate the antibiotic resistance of Helicobacter pylori (H. pylori) in outpatients and to explore the consistency between genotype and phenotype of H. pylori antibiotic resistance. A retrospective study on outpatients screened with urea breath test for H. pylori infection in Nanjing First Hospital from April 2018 to January 2022. Patients who tested positive underwent a consented upper endoscopy, and the H. pylori infection was confirmed by rapid urease test (RUT) and H. pylori culture. For antibiotic resistance phenotype analysis, the H. pylori strains isolated from gastric biopsy were tested for antibiotic resistance phenotype by the Kirby-Bauer disk diffusion test. In addition, the antibiotic resistance genotype of isolated H. pylori was tested with a real-time polymerase chain reaction. A total of 4,399 patients underwent H. pylori infection screening, and 3,306 H. pylori strains were isolated. The antibiotic resistance phenotype test revealed that the resistance rates of metronidazole (MTZ), clarithromycin (CLR), levofloxacin (LEV), amoxicillin (AMX), furazolidone (FR), and tetracycline (TE) were 74.58%, 48.61%, 34.83%, 0.76%, 0.27%, and 0.09%, respectively. Additionally, the antibiotic resistance genotype test revealed that rdxA gene mutation A610G (92.96%), A91G (92.95%), C92A (93.00%), and G392A (95.07%) were predominant in H. pylori with MTZ resistance; 23S rRNA gene mutation A2143G (86.47%) occurred in most H. pylori with CLR resistance; and gyrA gene mutation 87Ile/Lys/Tyr/Arg (97.32%) and 91Asn/Gly/Tyr (90.61%) were the most popular mutations in strains with LEV resistance. The phenotypic resistance and genotypic resistance to CLR (kappa value = 0.824) and LEV (kappa value = 0.895) were in good agreement. The history of eradication with MTZ, CLR, LEV, and AMX was correlated with H. pylori resistance. In short, this study demonstrated that drug resistance of H. pylori was mainly to MTZ, CLR, and LEV in local outpatients. Three drugs can be selected for increased MICs (Minimum Inhibitory Concentration) via single chromosomal mutations. In addition, the genotype could be used to predict the phenotypic H. pylori resistance to CLR and LEV. IMPORTANCE Helicobacter pylori is a key bacterium that causes stomach diseases. There was a high prevalence of H. pylori in the Chinese population. We analyzed the resistance phenotype and genotype characteristics of H. pylori in 4,399 outpatients at the First Hospital of Nanjing, China. We found a higher resistance rate to metronidazole (MTZ) , clarithromycin (CLR), and levofloxacin (LEV), and the genotype could be used to predict the phenotypic H. pylori resistance to CLR and LEV. This study provides information on H. pylori infection and also provides guidance for clinical doctors' drug treatment.
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Affiliation(s)
- Mengqiu Xiong
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | | | - Nida Khalid Ansari
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yalan Sun
- School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China
| | - Sijie Yin
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- Department of Laboratory Medicine, Yangzhou Hongquan Hospital, Yangzhou, China
| | - Lubanga Nasifu
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Huiling Sun
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Tao Xu
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Yuqin Pan
- General Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zhenlin Nie
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Caidong Liu
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zhenyu Zhang
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- H. pylori Research Key Laboratory, Nanjing Medical University, Nanjing, China
| | - Zongdan Jiang
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Shukui Wang
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- H. pylori Research Key Laboratory, Nanjing Medical University, Nanjing, China
| | - Bangshun He
- Department of Laboratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- H. pylori Research Key Laboratory, Nanjing Medical University, Nanjing, China
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9
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Chen TH, Chen MH, Hung YP, Chiang NJ, Huang KH, Lin YH, Lin RW, Chao Y, Li AFY, Yu HY, Hwang HE, Yeh YC, Wang YC, Fang WL. Elevated PD-L1 Expression and Microsatellite Instability in Elderly Patients With Gastric Cancer. J Immunother 2023; 46:111-119. [PMID: 36809276 DOI: 10.1097/cji.0000000000000458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 01/25/2023] [Indexed: 02/23/2023]
Abstract
Immunotherapy in combination with chemotherapy is the current treatment of choice for frontline programmed cell death ligand 1 (PD-L1)-positive gastric cancer. However, the best treatment strategy remains an unmet medical need for elderly or fragile patients with gastric cancer. Previous studies have revealed that PD-L1 expression, Epstein-Barr virus association, and microsatellite instability-high (MSI-H) are the potential predictive biomarkers for immunotherapy use in gastric cancer. In this study, we showed that PD-L1 expression, tumor mutation burden, and the proportion of MSI-H were significantly elevated in elderly patients with gastric cancer who were older than 70 years compared with patients younger than 70 years from analysis of The Cancer Genome Atlas gastric adenocarcinoma cohort [≥70/<70: MSI-H: 26.8%/15.0%, P =0.003; tumor mutation burden: 6.7/5.1 Mut/Mb, P =0.0004; PD-L1 mRNA: 5.6/3.9 counts per million mapped reads, P =0.005]. In our real-world study, 416 gastric cancer patients were analyzed and showed similar results (≥70/<70: MSI-H: 12.5%/6.6%, P =0.041; combined positive score ≥1: 38.1%/21.5%, P <0.001). We also evaluated 16 elderly patients with gastric cancer treated with immunotherapy and revealed an objective response of 43.8%, a median overall survival of 14.8 months, and a median progression-free survival of 7.0 months. Our research showed that a durable clinical response could be expected when treating elderly patients with gastric cancer with immunotherapy, and this approach is worth further study.
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Affiliation(s)
- Tien-Hua Chen
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Huang Chen
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Ping Hung
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Nai-Jung Chiang
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Kuo-Hung Huang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Lin
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ryan Weihsiang Lin
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yee Chao
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Anna Fen-Yau Li
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Pathology, and Laboratory Medicine Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hung-Yuan Yu
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Hospitalist ward, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsuen-En Hwang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Chen Yeh
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Pathology, and Laboratory Medicine Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Chao Wang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wen-Liang Fang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
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10
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Yang J, Xu J, Ling Z, Zhou X, Si Y, Liu X, Ji F. Prognostic effects of the gastric mucosal microbiota in gastric cancer. Cancer Sci 2023; 114:1075-1085. [PMID: 36403134 PMCID: PMC9986079 DOI: 10.1111/cas.15661] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 10/22/2022] [Accepted: 11/13/2022] [Indexed: 11/21/2022] Open
Abstract
Gastric cancer (GC) is one of the most common malignant tumors with a high incidence and mortality. Microbiota play a significant role in human health and disease. We aimed to investigate the prognostic value of the gastric microbiota in different stomach microhabitats. We used our previously published 16S rRNA gene sequence data. We retrospectively enrolled a cohort of 132 patients with GC with complete prognostic information and selected 78 normal tissues, 49 peritumoral tissues, and 112 tumoral tissues for microbiota analysis. Patients with different prognoses showed different gastric microbiota compositions and diversity. The association network of the abundant gastric microbiota was more complicated in patients with poor prognoses. In the peritumoral microhabitat of patients with good prognoses, Helicobacter was significantly increased, whereas Halomonas and Shewanella were significantly decreased relative to that in the peritumoral microhabitat of patients with poor prognoses. PiCRUSt analysis revealed that the peritumoral microbiota had more different Kyoto Encyclopedia of Genes and Genomes pathways than did the tumoral and normal microbiota. This study evaluated the long-term prognostic value of the gastric mucosal microbiota in patients with GC. These findings suggested that the characteristic alterations of the gastric mucosal microbiota may be markers for clinical outcomes in these patients.
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Affiliation(s)
- Jinpu Yang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Jiaren Xu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Zongxin Ling
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, Hangzhou, China
| | - Xinxin Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yongqiang Si
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Xiaosun Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Feng Ji
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
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11
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Noh JH, Shin JY, Lee JH, Park YS, Lee IS, Kim GH, Na HK, Ahn JY, Jung KW, Kim DH, Choi KD, Song HJ, Lee GH, Jung HY. Clinical Significance of Epstein-Barr Virus and Helicobacter pylori Infection in Gastric Carcinoma. Gut Liver 2023; 17:69-77. [PMID: 35611669 PMCID: PMC9840931 DOI: 10.5009/gnl210593] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 03/11/2022] [Accepted: 04/01/2022] [Indexed: 02/01/2023] Open
Abstract
Background/Aims Epstein-Barr virus (EBV) and Helicobacter pylori (HP) coinfection may synergistically induce severe inflammatory responses in the stomach tissue, increasing the risk of developing gastric cancer. We aimed to analyze the effect of EBV and HP coinfection on the clinicopathologic features and prognosis of gastric cancer, as well as to evaluate the role of EBV infection in non-gastric carcinoma with lymphoid stroma (non-GCLS). Methods Overall, 956 patients who underwent surgery for gastric cancer between September 2014 and August 2015 were eligible and divided into groups, according to GCLS morphology, EBV infection, and HP infection. Clinicopathologic characteristics and oncologic outcomes were analyzed retrospectively. Results EBV and HP coinfection was significantly associated with male sex, proximal location, GCLS morphology, and equivocal p53 expression (p<0.001). Multivariate analysis revealed that EBV infection alone (hazard ratio [HR], 0.362; 95% CI, 0.131 to 0.996; p=0.049) and lower third location (HR, 0.624; 95% CI, 0.413 to 0.943; p=0.025) were inversely correlated with overall survival. During median follow-up period of 72 months, overall survival rate was not significantly different between the EBV and HP coinfection group and others (97.6% vs 86.8%; log-rank p=0.144). In non-GCLS patients (n=920), overall survival rate was not significantly different between the EBV infection group and others (96.9% vs 86.4%; log-rank p=0.126). Conclusions EBV and HP coinfection is not an independent prognostic factor for gastric cancer. EBV infection status, regardless of HP infection, affects the clinicopathologic features of all types of gastric cancer. However, it does not lead to a significant difference in overall survival of non-GCLS patients.
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Affiliation(s)
- Jin Hee Noh
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun Young Shin
- Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Hoon Lee
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea,Corresponding AuthorJeong Hoon Lee, ORCIDhttps://orcid.org/0000-0002-0778-7585, E-mail
| | - Young Soo Park
- Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea,Young Soo Park, ORCIDhttps://orcid.org/0000-0001-5389-4245, E-mail
| | - In-Seob Lee
- Departments of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ga Hee Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Hee Kyong Na
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Yong Ahn
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Wook Jung
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kee Don Choi
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ho June Song
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gin Hyug Lee
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hwoon-Yong Jung
- Departments of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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12
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Chen MC, Su HY, Su YH, Huang KH, Fang WL, Lin CW, Chen MH, Chao Y, Lo SS, Fen-Yau Li A, Wu CW. The clinicopathological and genetic differences among gastric cancer patients with no recurrence, early recurrence, and late recurrence after curative surgery. J Chin Med Assoc 2023; 86:57-64. [PMID: 36374529 DOI: 10.1097/jcma.0000000000000846] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND To date, few reports have investigated the genetic alterations and clinicopathological features among gastric cancer (GC) patients with no tumor recurrence, early recurrence, and late recurrence following curative surgery. METHODS A total of 473 GC patients undergoing curative surgery were included. The clinicopathological characteristics, patient prognosis, recurrence patterns, and genetic alterations were compared between GC patients with early recurrence and late recurrence. RESULTS Among the 473 GC patients, 119 had early recurrence (<2 years) and 45 had late recurrence (≥2 years). Patients with early recurrence had tumor size larger than 5 cm, fewer superficial-type tumors, more lymphovascular invasion, more advanced pathological T and N categories and Tumor, Node, Metastasis (TNM) stages, and worse 5-year overall survival than patients with late recurrence and no recurrence. For intestinal-type GC, patients with no tumor recurrence had more Helicobacter pylori infection than patients with early recurrence and late recurrence; for diffuse-type GC patients, the frequency of PIK3CA amplification was the highest in early recurrence, followed by late recurrence and no recurrence. GC patients with single-site recurrence had more ARID1A mutations than those with multiple-site recurrence. Multivariate analysis demonstrated that age, tumor recurrence, and pathological N categories were independent prognostic factors. CONCLUSION PIK3CA amplifications were more common in diffuse-type GC with early recurrence, whereas ARID1A mutations were more common in patients with single-site recurrence. Targeted therapy and immunotherapy might be helpful for these patients.
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Affiliation(s)
- Meng-Chao Chen
- Department of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, ROC
- Department of Neurosurgery, China Medical University Hospital, Taipei Branch, Taipei, Taiwan, ROC
| | - Hsuan-Yu Su
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yen-Hao Su
- Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
- Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan, ROC
- Division of General Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan, ROC
| | - Kuo-Hung Huang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Gastric Cancer Medical Center, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Wen-Liang Fang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Gastric Cancer Medical Center, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chii-Wann Lin
- Department of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, ROC
| | - Ming-Huang Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yee Chao
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Su-Shun Lo
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Surgery, National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan, ROC
| | - Anna Fen-Yau Li
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chew-Wun Wu
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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13
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Helicobacter Pylori and Gastric Cancer Progression. Curr Microbiol 2022; 79:383. [PMID: 36329283 DOI: 10.1007/s00284-022-03089-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 10/13/2022] [Indexed: 11/06/2022]
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14
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Ghojazadeh M, Somi MH, Naseri A, Salehi-Pourmehr H, Hassannezhad S, Hajikamanaj Olia A, Kafshdouz L, Nikniaz Z. Systematic Review and Meta-analysis of TP53, HER2/ERBB2, KRAS, APC, and PIK3CA Genes Expression Pattern in Gastric Cancer. Middle East J Dig Dis 2022; 14:335-345. [PMID: 36619267 PMCID: PMC9489438 DOI: 10.34172/mejdd.2022.292] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 05/19/2022] [Indexed: 11/06/2022] Open
Abstract
Background: With a global prevalence of about 10%, gastric cancer is among the most prevalent cancers. Currently, there has been an ongoing trend toward investigating genetic disruptions in different cancers because they can be used as a target-specific therapy. We aimed to systemically review some gene expression patterns in gastric cancer. Methods: The current systematic review was designed and executed in 2020. Scopus, PubMed, Cochrane Library, Google Scholar, web of knowledge, and Science Direct were searched for relevant studies. A manual search of articles (hand searching), reference exploring, checking for grey literature, and seeking expert opinion were also done. Results: In this review, 65 studies were included, and the expression pattern of HER2/ ERBB2, ER1/Erb1/EGFR, PIK3CA, APC, KRAS, ARID1A, TP53, FGFR2 and MET was investigated. TP53, APC, KRAS, and PIK3CA mutation cumulative frequency were 24.8 (I2=95.05, Q value=525.53, df=26, P<0.001), 7.2 (I2=89.79, Q value=48.99, df=5, P<0.001), 7.8 (I2=93.60, Q value=140.71, df=9, P=0.001) and 8.6 (I2=80.78, Q value=525.53, df=9, P<0.001) percent, respectively. Overexpression was investigated for HER1/ Erb1/EGFR, PIK3CA, APC, KRAS, ARID1A, TP53, CCND1, FGFR2, MET and MYC. The frequency of TP53 and HER2/ERBB2 were 43.1 (I2=84.06, Q value=58.09, df=9, P<0.001) and 20.8 (I2=93.61, Q value=234.89, df=15, P<0.001) percent, respectively. Conclusion: More research is encouraged to investigate the genes for which we could not perform a meta-analysis.
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Affiliation(s)
- Morteza Ghojazadeh
- Research Center for Evidence-based Medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohammad Hossein Somi
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amirreza Naseri
- Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hanieh Salehi-Pourmehr
- Research Center for Evidence-based Medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sina Hassannezhad
- Research Center for Evidence-based Medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Arash Hajikamanaj Olia
- Research Center for Evidence-based Medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Tabriz, Iran,Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Kafshdouz
- Genetic Department, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zeinab Nikniaz
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran,Corresponding Author: Zeinab Nikniaz, PhD Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Tel:+98 4133367473 Fax:+984133367473
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15
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Jia Z, Zheng M, Jiang J, Cao D, Wu Y, Zhang Y, Fu Y, Cao X. Positive H. pylori status predicts better prognosis of non-cardiac gastric cancer patients: results from cohort study and meta-analysis. BMC Cancer 2022; 22:155. [PMID: 35135494 PMCID: PMC8822753 DOI: 10.1186/s12885-022-09222-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 01/21/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Previous researches have associated Helicobacter pylori (H. pylori) with a prognosis of gastric cancer (GC), however, without a concert conclusion. This study aimed to study this issue further by a prospective cohort study and a meta-analysis. METHODS Histologically diagnosed gastric cancer (GC) patients were recruited into the primary prospective cohort study between January 2009 to December 2013. All the patients were followed-up periodically to record information on post-surgery therapy and overall survival status. The pre-surgery status of H. pylori was measured by enzyme-linked immunosorbent assay. A meta-analysis was conducted after retrieving related researches in the databases of PubMed and Embase up to April 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and the survival time of GC patients. I2 statistics and Q test were used to assess the heterogeneity. Sensitivity analyses were performed using Galbraith's plot, leave-one-out analysis, subgroup analyses and meta-regression to explore the sources of heterogeneity and the stability of the summary results. RESULTS A total of 743 GC patients with radical tumorectomy were included prospectively and 516 (69.4%) were positive on H. pylori. H. pylori-positive patients tended to survive longer than -negative ones (HR 0.92, 95%CI: 0.74-1.15), though the tendency was not statistically significant. Cohort studies on the prognosis of GC were retrieved comprehensively by assessing the full-text and 59 published studies, together with the result of our study, were included in the further meta-analysis. The summarized results related the positive status of H. pylori to better overall survival (HR 0.81, 95%CI: 0.72-0.90) and disease-free survival (HR 0.83, 95%CI: 0.67-0.99). Results from subgroup analyses indicated that the pooled magnitude of this association was relatively lower in studies not referring to H. pylori in title and abstract. CONCLUSIONS In conclusion, gastric cancer patients with H. pylori have a better prognosis than patients of H. pylori negative. More stringent surveillance strategies may be necessary for patients with H. pylori negative at cancer diagnosis.
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Affiliation(s)
- Zhifang Jia
- Division of Clinical Research, The First Hospital of Jilin University, Changchun, China
| | - Min Zheng
- Division of Clinical Research, The First Hospital of Jilin University, Changchun, China
| | - Jing Jiang
- Division of Clinical Research, The First Hospital of Jilin University, Changchun, China.,Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Donghui Cao
- Division of Clinical Research, The First Hospital of Jilin University, Changchun, China
| | - Yanhua Wu
- Division of Clinical Research, The First Hospital of Jilin University, Changchun, China
| | - Yuzheng Zhang
- Division of Clinical Research, The First Hospital of Jilin University, Changchun, China.,Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China
| | - Yingli Fu
- Division of Clinical Research, The First Hospital of Jilin University, Changchun, China
| | - Xueyuan Cao
- Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, China.
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16
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Senchukova MA, Tomchuk O, Shurygina EI. Helicobacter pylori in gastric cancer: Features of infection and their correlations with long-term results of treatment. World J Gastroenterol 2021; 27:6290-6305. [PMID: 34712033 PMCID: PMC8515796 DOI: 10.3748/wjg.v27.i37.6290] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 06/21/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is a spiral-shaped bacterium responsible for the development of chronic gastritis, gastric ulcer, gastric cancer (GC), and MALT-lymphoma of the stomach. H. pylori can be present in the gastric mucosa (GM) in both spiral and coccoid forms. However, it is not known whether the severity of GM contamination by various vegetative forms of H. pylori is associated with clinical and morphological characteristics and long-term results of GC treatment.
AIM To establish the features of H. pylori infection in patients with GC and their correlations with clinical and morphological characteristics of diseases and long-term results of treatment.
METHODS Of 109 patients with GC were included in a prospective cohort study. H. pylori in the GM and tumor was determined by rapid urease test and by immunohistochemically using the antibody to H. pylori. The results obtained were compared with the clinical and morphological characteristics and prognosis of GC. Statistical analysis was performed using the Statistica 10.0 software.
RESULTS H. pylori was detected in the adjacent to the tumor GM in 84.5% of cases, of which a high degree of contamination was noted in 50.4% of the samples. Coccoid forms of H. pylori were detected in 93.4% of infected patients, and only coccoid-in 68.9%. It was found that a high degree of GM contamination by the coccoid forms of H. pylori was observed significantly more often in diffuse type of GC (P = 0.024), in poorly differentiated GC (P = 0.011), in stage T3-4 (P = 0.04) and in N1 (P = 0.011). In cases of moderate and marked concentrations of H. pylori in GM, a decrease in 10-year relapse free and overall survival from 55.6% to 26.3% was observed (P = 0.02 and P = 0.07, respectively). The relationship between the severity of the GM contamination by the spiral-shaped forms of H. pylori and the clinical and morphological characteristics and prognosis of GC was not revealed.
CONCLUSION The data obtained indicates that H. pylori may be associated not only with induction but also with the progression of GC.
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Affiliation(s)
- Marina A Senchukova
- Department of Oncology, Orenburg State Medical University, Orenburg 460000, Russia
| | - Olesya Tomchuk
- Department of Histology, Cytology, Embryology, Orenburg State Medical University, Orenburg 460000, Russia
| | - Elena I Shurygina
- Department of Pathology, Orenburg State Medical University, Orenburg 460000, Russia
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17
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Pai SM, Huang KH, Chen MH, Fang WL, Chao Y, Lo SS, Li AFY, Wu CW, Shyr YM. Cardia Gastric Cancer Is Associated With Increased PIK3CA Amplifications and HER2 Expression Than Noncardia Gastric Cancer According to Lauren Classification. Front Oncol 2021; 11:632609. [PMID: 34168977 PMCID: PMC8217656 DOI: 10.3389/fonc.2021.632609] [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: 11/23/2020] [Accepted: 05/17/2021] [Indexed: 12/02/2022] Open
Abstract
Background To date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC). Methods In total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients. Results Among the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, P = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, P = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased PIK3CA amplification than in patients with intestinal-type GC and was associated with increased HER2 expression in patients with diffuse-type GC. Conclusions Cardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, PIK3CA amplification was more common, and in those with diffuse-type GC, HER2 expression was more common. Targeted therapy may be beneficial for these patient subgroups.
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Affiliation(s)
- Shih-Min Pai
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Kuo-Hung Huang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Huang Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wen-Liang Fang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yee Chao
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Su-Shun Lo
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Surgery, National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan
| | - Anna Fen-Yau Li
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chew-Wun Wu
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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18
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Hsu LW, Huang KH, Chen MH, Fang WL, Chao Y, Lo SS, Li AFY, Wu CW, Shyr YM. Genetic alterations in gastric cancer patients according to sex. Aging (Albany NY) 2020; 13:376-388. [PMID: 33288737 PMCID: PMC7835020 DOI: 10.18632/aging.202142] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 10/09/2020] [Indexed: 02/06/2023]
Abstract
To date, few reports have investigated the genetic alterations and clinicopathological features in gastric cancer (GC) according to sex. In total, 2673 GC patients receiving curative surgery were enrolled. Among the 2673 GC patients, 1979 (74.0%) patients were male. After propensity-score matching, 846 patients were enrolled for the analysis, including 423 males and 423 females. There was no significant difference in the clinicopathological features between the sexes. Regarding the initial recurrence pattern, the males were more likely to develop tumor recurrence and liver metastasis than the females, especially in stage III GC. Regarding the molecular analysis, the males had higher PD-L1 expression than the females, especially in stage III GC. In addition, the patients aged ≥ 65 years had higher PD-L1 expression than the patients younger than 65 years. The multivariate analysis demonstrated that sex was among the independent prognostic factors affecting overall survival (OS) and disease-free survival (DFS). Among the patients with liver metastases, PD-L1 expression was more common among the aged male patients. The males were associated with more tumor recurrence and higher PD-L1 expression than the females, especially in stage III GC. For GC patients with liver metastases, PD-L1 testing is recommended, especially among aged male patients.
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Affiliation(s)
- Li-Wen Hsu
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Kuo-Hung Huang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Huang Chen
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wen-Liang Fang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yee Chao
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Su-Shun Lo
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,National Yang-Ming University Hospital, Yilan, Taiwan
| | - Anna Fen-Yau Li
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chew-Wun Wu
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang-Ming University, Taipei, Taiwan
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19
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The clinicopathological characteristics and genetic alterations of gastric cancer patients according to the Lauren classification. Int Surg 2020. [DOI: 10.9738/intsurg-d-20-00022.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
ObjectiveThe Lauren classification is an important histological classification of gastric cancer (GC) with different biological behaviors between histological types.BackgroundTo date, there are few reports on the genetic alterations and survival differences between different histological types according to the Lauren classification.MethodsIn total, 433 GC patients undergoing surgery were enrolled. The clinicopathological features, prognoses, and genetic alterations of the different Lauren types were compared.ResultsDiffuse-type GC was associated with a younger age, female predominance, more Borrmann type 3 and 4 tumors, more advanced pathological tumor (T) and node (N) categories, more tumor recurrences (especially peritoneal recurrence), and worse 5-year overall survival and disease-free survival rates than intestinal-type GC and mixed-type GC. Regarding genetic alterations, mixed-type GC was associated with more TP53 mutations than intestinal-type GC and diffuse-type GC. Multivariate analysis demonstrated the following independent prognostic factors: age, Lauren classification, and pathological T and N categories. Regarding mixed-type GC, diffuse-type major tumors were associated with more lymphovascular invasion, a more advanced N category and TNM stage, and fewer PI3K/AKT pathway mutations than intestinal-type major tumors.ConclusionsDiffuse-type GC had unfavorable clinicopathological features and a worse prognosis than intestinal-type GC. For mixed-type GC, the clinicopathological features and genetic alterations were different between intestinal-type major tumors and diffuse-type major tumors.
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20
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Wu CW, Chen MH, Huang KH, Chang SC, Fang WL, Lin CH, Chao Y, Lo SS, Li AFY, Shyr YM. The clinicopathological characteristics and genetic alterations between younger and older gastric cancer patients with curative surgery. Aging (Albany NY) 2020; 12:18137-18150. [PMID: 32961530 PMCID: PMC7585087 DOI: 10.18632/aging.103627] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 06/22/2020] [Indexed: 01/24/2023]
Abstract
Few reports have investigated different genetic alterations according to age in various cancers. In total, 1749 GC patients receiving curative surgery were enrolled. The clinicopathological features, and prognoses were compared between younger (<65 years) and older (≥65 years) patients. Genetic mutations were analyzed using mass spectrometric single nucleotide polymorphism genotyping technology, including 68 validated mutations within eight genes (TP53, ARID1A, BRAF, and the PI3K/AKT pathway) previously reported in relation to age. Younger patients were more likely to be female and have poor cell differentiation, diffuse-type tumors, less lymphovascular invasion, fewer liver metastases, and better 5-year overall survival (OS) (68.0% vs. 54.6%, P<0.001) and disease-free survival (DFS) (65.4% vs. 53.0%, P<0.001) rates than older patients. Regarding the genetic alterations, older patients had more microsatellite instability-high (MSI-H) tumors and more ARID1A mutations than younger patients. Younger patients had significantly better OS and DFS rates than older patients for each pathological Tumor, Node, Metastasis (TNM) stage. Older patients had a significantly higher non-cancer related death rate than younger patients (36.2% vs. 12.3%, P<0.001). Age was an independent prognostic factor in GC. In conclusion, age was associated with different clinicopathological features and genetic alterations in GC with curative surgery.
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Affiliation(s)
- Chew-Wun Wu
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Huang Chen
- School of Medicine, National Yang-Ming University, Taipei, Taiwan,Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Kuo-Hung Huang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Shih-Ching Chang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan,Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wen-Liang Fang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan,School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chien-Hsing Lin
- Genome Research Center, National Yang-Ming University, Taipei, Taiwan
| | - Yee Chao
- School of Medicine, National Yang-Ming University, Taipei, Taiwan,Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Su-Shun Lo
- School of Medicine, National Yang-Ming University, Taipei, Taiwan,National Yang-Ming University Hospital, Yilan, Taiwan
| | - Anna Fen-Yau Li
- School of Medicine, National Yang-Ming University, Taipei, Taiwan,Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan,School of Medicine, National Yang-Ming University, Taipei, Taiwan
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21
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The Clinicopathological Characteristics And Genetic Alterations of Signet-ring Cell Carcinoma in Gastric Cancer. Cancers (Basel) 2020; 12:cancers12082318. [PMID: 32824568 PMCID: PMC7463705 DOI: 10.3390/cancers12082318] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 08/04/2020] [Accepted: 08/12/2020] [Indexed: 02/08/2023] Open
Abstract
Signet-ring cell carcinoma (SRC) in advanced gastric cancer (GC) is often associated with more invasiveness and a worse prognosis than other cell types. The genetic alterations associated with gastric carcinogenesis in SRC are still unclear. In this study, 441 GC patients receiving curative surgery for GC between 2005 and 2013 were enrolled. The clinicopathological characteristics and genetic alterations of GC patients with and without SRC were compared. Among the 441 GC patients, 181 had SRC. For early GC, patients with SRC had more tumors located in the middle and lower stomach, more infiltrating tumors and better overall survival (OS) rates than those without SRC. For advanced GC, patients with SRC had more scirrhous type tumors, more PIK3CA amplifications, fewer microsatellite instability-high (MSI-H) tumors, more peritoneal recurrences and worse 5-year OS rates than those without SRC. For advanced GC with SRC, patients with peritoneal recurrence tended to have PD-L1 expression. For advanced GC without SRC, patients with liver metastasis tended to have PD-L1 expression, PI3K/AKT pathway mutations, TP53 mutations and MSI-H tumors. For advanced GC, PD-L1 expression was associated with peritoneal recurrence in SRC tumors, while non-SRC tumors with liver metastasis were likely to have PI3K/AKT pathway mutations, TP53 mutations and PD-L1 expression; immunotherapy and targeted therapy may be beneficial for these patients.
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22
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Dos Santos Pereira E, Magalhães Albuquerque L, de Queiroz Balbino V, da Silva Junior WJ, Rodriguez Burbano RM, Pordeus Gomes JP, Barem Rabenhorst SH. Helicobacter pylori cagE, cagG, and cagM can be a prognostic marker for intestinal and diffuse gastric cancer. INFECTION GENETICS AND EVOLUTION 2020; 84:104477. [PMID: 32736040 DOI: 10.1016/j.meegid.2020.104477] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 07/21/2020] [Accepted: 07/23/2020] [Indexed: 01/15/2023]
Abstract
It is known that Helicobacter pylori is the main cause of peptic ulceration and gastric cancer. However, there is a lack of information on whether H. pylori strains may differ in gastric cancer histological subtypes. This study aimed to investigate different H. pylori strains considering six cag Pathogenicity Island - cagPAI genes (cagA, cagE, cagG, cagM, cagT, and virb11), and vacuolating cytotoxin - vacA alleles, and their relation to gastric cancer histologic subtypes. For this purpose, tumor samples from 285 patients with gastric carcinoma were used. H. pylori infection and genotypes were determined by polymerase chain reaction (PCR). H. pylori was detected in 93.9% of gastric tumors. For comparative analyzes between histopathological subtypes considering H. pylori cagPAI genes the strains were grouped according to the vacA s1/s2 alleles. In the vacAs1 group, the strains cagA(-)cagE(+), cagA(+)cagE(+)cagG(+), cagA(+)cagM(+), or only cagE(+) strains were more frequent in the intestinal subtype (P = .009; P = .024; P = .046, respectively). In contrast, cagM(+)cagG(+)cagA(-) and cagE(-) were associated with diffuse tumors (P = .036), highlighting the presence of cagE in the development of intestinal tumors, and the presence of cagG and absence of cagE in diffuse tumors. Furthermore, WEKA software and Decision Tree (CART) analyses confirmed these findings, in which cagE presence was associated with intestinal tumors, and cagE absence and cagG(+) with diffuse tumors. In conclusion our results showed that vacAs1 (cagG + cagM) strains, mainly cagG positive with cagE absence, were relevant in the studied population for the diffuse outcome, while the presence of cagE was relevant for the intestinal outcome. These findings suggest the relevance of these H. pylori genes as potential markers for gastric cancer histological outcomes.
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Affiliation(s)
- Eliane Dos Santos Pereira
- Department of Pathology and Forensic Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil
| | | | - Valdir de Queiroz Balbino
- Department of Genetics, Biomedical Center, Federal University of Pernambuco, Recife, Pernambuco, Brazil
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23
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Fang WL, Chen MH, Huang KH, Lin CH, Chao Y, Lo SS, Li AFY, Wu CW, Shyr YM. The Clinicopathological Features and Genetic Alterations in Epstein-Barr Virus-Associated Gastric Cancer Patients after Curative Surgery. Cancers (Basel) 2020; 12:cancers12061517. [PMID: 32531970 PMCID: PMC7352714 DOI: 10.3390/cancers12061517] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2020] [Revised: 06/06/2020] [Accepted: 06/07/2020] [Indexed: 12/20/2022] Open
Abstract
Background: Epstein–Barr virus (EBV)-associated gastric cancer (GC) is one of four major gastric cancer types and is traditionally considered to be related to lymphoepithelioma-like GC. Few studies have investigated the clinical significance of EBV infection in intestinal/solid type, diffuse (poorly cohesive) type, and lymphoepithelioma-like GC. Methods: A total of 460 GC patients receiving curative surgery were enrolled. The clinicopathological features, genetic alterations and prognoses were compared between patients with and without EBV infection. Results: EBV-positive GC patients (n = 43) had more tumors located in the upper and middle stomach, more common in lymphoepithelioma-like carcinoma, more lymphoid stroma, fewer Helicobacter pylori infections, and higher programmed death-ligand 1 (PD-L1) expression than EBV-negative GC patients. For intestinal/solid type GC, EBV-positive tumors were more likely to be located in the upper and middle stomach, have more lymphoid stroma, fewer Helicobacter pylori infections, higher PD-L1 expression, and more liver metastases than EBV-negative tumors. For diffuse (poorly cohesive) type GC, EBV-positive tumors were more likely to be located in the upper stomach, and have more lymphoid stroma than EBV-negative tumors. For lymphoepithelioma-like GC, EBV-positive tumors had more PI3K/AKT pathway mutations than EBV-negative tumors. Conclusions: Intestinal/solid type GC patients with EBV-positive tumors were associated with higher PD-L1 expression and more liver metastases, while lymphoepithelioma-like GC patients with EBV-positive tumors had more PI3K/AKT pathway mutations. Immunotherapy and targeted therapy may be beneficial for these groups of patients. Routine EBV survey is recommended in GC.
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Affiliation(s)
- Wen-Liang Fang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (K.-H.H.); (C.-W.W.); (Y.-M.S.)
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; (M.-H.C.); (Y.C.); (S.-S.L.); (A.F.-Y.L.)
- Correspondence:
| | - Ming-Huang Chen
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; (M.-H.C.); (Y.C.); (S.-S.L.); (A.F.-Y.L.)
- Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
| | - Kuo-Hung Huang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (K.-H.H.); (C.-W.W.); (Y.-M.S.)
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; (M.-H.C.); (Y.C.); (S.-S.L.); (A.F.-Y.L.)
| | - Chien-Hsing Lin
- Genome Research Center, National Yang-Ming University, Taipei 11221, Taiwan;
| | - Yee Chao
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; (M.-H.C.); (Y.C.); (S.-S.L.); (A.F.-Y.L.)
- Center of Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
| | - Su-Shun Lo
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; (M.-H.C.); (Y.C.); (S.-S.L.); (A.F.-Y.L.)
- Department of Surgery, National Yang-Ming University Hospital, Yilan 26058, Taiwan
| | - Anna Fen-Yau Li
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; (M.-H.C.); (Y.C.); (S.-S.L.); (A.F.-Y.L.)
- Department of Pathology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
| | - Chew-Wun Wu
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (K.-H.H.); (C.-W.W.); (Y.-M.S.)
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; (M.-H.C.); (Y.C.); (S.-S.L.); (A.F.-Y.L.)
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (K.-H.H.); (C.-W.W.); (Y.-M.S.)
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan; (M.-H.C.); (Y.C.); (S.-S.L.); (A.F.-Y.L.)
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24
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The Clinicopathological Features and Genetic Mutations in Gastric Cancer Patients According to EMAST and MSI Status. Cancers (Basel) 2020; 12:cancers12030551. [PMID: 32120855 PMCID: PMC7139949 DOI: 10.3390/cancers12030551] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 02/22/2020] [Accepted: 02/25/2020] [Indexed: 01/22/2023] Open
Abstract
Background: There has been no report regarding the clinicopathological features and genetic mutations regarding elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in gastric cancer (GC). Methods: The correlation among EMAST status, microsatellite instability (MSI) status, mutations of common GC-related genes and 16 DNA repair-associated genes, and the clinicopathological features were analyzed. Results: Among the 360 GC patients enrolled, there were 76 (21.1%) with EMAST+ tumors and 284 with EMAST− tumors, and 59 (16.4%) were MSI-high (MSI-H) tumors, and 301 were microsatellite stable (MSS) tumors. Patients with EMAST+ tumors exhibited an earlier pathological T category and had more genetic mutations in the PI3K/AKT pathway, ARID1A and DNA repair-associated genes than those with EMAST− tumors. Patients with MSI-H tumors have more genetic mutations in the PI3K/AKT pathway and DNA repair-associated genes than those with MSS tumors. In the subgroup analysis for MSI-H GC, EMAST+ tumors were associated with earlier pathological T and N categories, earlier TNM stages, higher frequency of DNA-repair-associated genetic mutations, and a better survival rate than EMAST− tumors. Conclusions:PI3K/AKT pathway mutations may play an important role in EMAST+ and/or MSI-H GC. EMAST+/MSI-H tumors seem to represent a different subtype of gastric cancer from EMAST−/MSI-H tumors.
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25
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Tseng CH, Fang WL, Huang KH, Chen MH, Chao Y, Lo SS, Li AFY, Wu CW, Shyr YM. The clinicopathological characteristics and genetic alterations of mucinous carcinoma of the stomach. J Chin Med Assoc 2020; 83:141-147. [PMID: 32015267 DOI: 10.1097/jcma.0000000000000232] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Mucinous gastric carcinoma (MGC) is rare and often associated with an advanced stage. The clinicopathological features and prognosis of MGC and non-MGC (NMGC) are controversial. METHODS In total, 2637 gastric cancer (GC) patients receiving curative surgery were enrolled. The clinicopathological features and genetic alterations were compared between patients with MGC and NMGC. RESULTS Among the 2637 GC patients, 92 (3.5%) had MGC. After propensity score matching, compared to patients with NMGC, patients with MGC had more poorly differentiated tumors, medullary stromal reaction-type tumors, tumors with infiltrating Ming's classification, diffuse-type tumors, more abnormal preoperative serum carbohydrate antigen 19-9 levels, and more advanced T categories. After propensity score matching, there were no significant differences between MGC and NMGC regarding the initial recurrence patterns, 5-year overall survival (OS), and disease-free survival (DFS) rates. Multivariate analysis demonstrated that the MGC cell type is not an independent prognostic factor of OS and DFS. No significant differences in microsatellite instability status, Epstein-Barr virus infection, Helicobacter pylori infection, or genetic mutations were observed between MGC and NMGC. The expression of programmed death-ligand 1 (PD-L1) was significantly higher in MGC than that in NMGC. MGC was diagnosed at a more advanced stage compared with NMGC. CONCLUSION MGC itself was not an independent prognostic factor of worse survival. MGC was correlated with higher PD-L1 expression than NMGC, which may have a clinical impact on the treatment of MGC in the future.
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Affiliation(s)
- Chien-Hsun Tseng
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Wen-Liang Fang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Kuo-Hung Huang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Ming-Huang Chen
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yee Chao
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Su-Shun Lo
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- National Yang-Ming University Hospital, Yilan, Taiwan, ROC
| | - Anna Fen-Yau Li
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chew-Wun Wu
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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26
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Fang WL, Chen MH, Huang KH, Chang SC, Lin CH, Chao Y, Lo SS, Li AFY, Wu CW, Shyr YM. Analysis of the clinical significance of DNA methylation in gastric cancer based on a genome-wide high-resolution array. Clin Epigenetics 2019; 11:154. [PMID: 31675985 PMCID: PMC6824057 DOI: 10.1186/s13148-019-0747-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 09/22/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Aberrant DNA methylation is involved in gastric carcinogenesis and may serve as a useful biomarker in the diagnosis and detection of gastric cancer (GC) recurrence. RESULTS A total of 157 patients who received surgery for GC were enrolled in the present study. A genome-wide methylation analysis was performed in tumor and adjacent normal tissues for the discovery set of 16 GC patients; the top three hypermethylated CpG sites of DNA promoters were selected for validation in tissue and plasma samples for the validation set of 141 GC patients. The frequencies of the top three hypermethylated genes in available patient tissues (n = 141) and plasma samples (n = 106) were 41.8% and 38.7%, respectively, for ADAM19; 40.4% and 42.5%, respectively, for FLI1; and 56.7% and 50.9%, respectively, for MSC. In both tissue and plasma samples, FLI1 hypermethylation was associated with more advanced GC and liver and distant lymphatic metastasis, and ADAM19 hypermethylation was associated with more stage IV GC. In plasma samples, MSC hypermethylation was more common in non-superficial type GC than samples without MSC hypermethylation. In both tissue and plasma samples, patients with methylation of all the three genes had significantly more liver metastases, distant lymphatic metastases, and paraaortic lymph node metastases than patients with two or fewer hypermethylated genes. The survival analysis showed that only for stage III GC, patients with hypermethylation of two or three genes had a worse 5-year disease-free survival rate than those with hypermethylation of one or none of the three genes. Subgroup analysis showed that FLI1 hypermethylation in both tissue and plasma samples was associated with liver metastasis in MSI-/EBV- GC, and MSC hypermethylation in tissue samples was correlated with liver metastasis in MSI+ or EBV+ GC. Patients with FLI1 hypermethylation in plasma samples had a significantly worse 5-year disease-free survival rate than those without FLI1 hypermethylation in MSI-/EBV- GC. FLI1 hypermethylation was an independent prognostic factor affecting the overall survival and disease-free survival in both tissue and plasma samples. CONCLUSIONS DNA methylation is a useful biomarker for predicting tumor recurrence patterns and GC patient survival.
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Affiliation(s)
- Wen-Liang Fang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd, Beitou District, Taipei City, Taiwan, 11217. .,School of Medicine, National Yang-Ming University, Taipei City, Taiwan, 11217.
| | - Ming-Huang Chen
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan, 11217.,Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan, 11217
| | - Kuo-Hung Huang
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd, Beitou District, Taipei City, Taiwan, 11217.,School of Medicine, National Yang-Ming University, Taipei City, Taiwan, 11217
| | - Shih-Ching Chang
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan, 11217.,Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan, 11217
| | - Chien-Hsing Lin
- Genome Research Center, National Yang-Ming University, Taipei City, Taiwan, 11217
| | - Yee Chao
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan, 11217.,Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan, 11217
| | - Su-Shun Lo
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan, 11217.,National Yang-Ming University Hospital, Yilan County, Taiwan, 26058
| | - Anna Fen-Yau Li
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan, 11217.,Department of Pathology, Taipei Veterans General Hospital, Taipei City, 11217, Taiwan
| | - Chew-Wun Wu
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd, Beitou District, Taipei City, Taiwan, 11217.,School of Medicine, National Yang-Ming University, Taipei City, Taiwan, 11217
| | - Yi-Ming Shyr
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd, Beitou District, Taipei City, Taiwan, 11217.,School of Medicine, National Yang-Ming University, Taipei City, Taiwan, 11217
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27
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Chang C, Wang H, Liu J, Pan C, Zhang D, Li X, Pan Y. Porphyromonas gingivalis Infection Promoted the Proliferation of Oral Squamous Cell Carcinoma Cells through the miR-21/PDCD4/AP-1 Negative Signaling Pathway. ACS Infect Dis 2019; 5:1336-1347. [PMID: 31243990 DOI: 10.1021/acsinfecdis.9b00032] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Recent epidemiological studies have revealed that Porphyromonas gingivalis, a major pathogen in periodontal disease, is associated with the development of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms induced by P. gingivalis have not been well-defined. We aimed to determine the role of P. gingivalis in OSCC proliferation and the relevant molecular mechanisms. A cellular proliferation model of OSCC Tca8113 cells infected by P. gingivalis at a multiplicity of infection (MOI) of 50 was established. Cell proliferation was drastically increased in the infected cells compared with the control cells, while the proportion of cells in S phase was increased and the proportion of cells in G1 phase was decreased in the infected cells compared with the control cells. Additionally, the levels of activator protein 1 (AP-1; c-Jun and c-Fos) and its target gene cyclin D1 were increased in P. gingivalis-infected Tca8113 cells compared with control cells. miR-21 expression was elevated when programmed cell death 4 (PDCD4) expression was downregulated. Cyclin D1 expression was regulated by miR-21, PDCD4, and AP-1. The disruption of the pathway by silencing c-Jun, blocking miR-21 expression, or overexpressing PDCD4 led to decreased cyclin D1 expression and inhibited cell proliferation. P. gingivalis DNA levels were positively correlated with miR-21 and c-Jun expression and negatively correlated with PDCD4 expression in clinical OSCC samples. Our findings indicated that P. gingivalis might promote OSCC proliferation by regulating cyclin D1 expression via the miR-21/PDCD4/AP-1 negative feedback signaling pathway.
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Affiliation(s)
- Chunrong Chang
- Department of Periodontics, School of Stomatology, China Medical University, No. 117 Nanjing North Street, Shenyang, Liaoning 110002, China
| | - Hongyan Wang
- Department of Periodontics, School of Stomatology, China Medical University, No. 117 Nanjing North Street, Shenyang, Liaoning 110002, China
| | - Junchao Liu
- Department of Periodontics, School of Stomatology, China Medical University, No. 117 Nanjing North Street, Shenyang, Liaoning 110002, China
| | - Chunling Pan
- Department of Periodontics, School of Stomatology, China Medical University, No. 117 Nanjing North Street, Shenyang, Liaoning 110002, China
| | - Dongmei Zhang
- Department of Periodontics, School of Stomatology, China Medical University, No. 117 Nanjing North Street, Shenyang, Liaoning 110002, China
| | - Xin Li
- Department of Periodontics, School of Stomatology, China Medical University, No. 117 Nanjing North Street, Shenyang, Liaoning 110002, China
| | - Yaping Pan
- Department of Periodontics, School of Stomatology, China Medical University, No. 117 Nanjing North Street, Shenyang, Liaoning 110002, China
- Department of Oral Biology, School of Stomatology, China Medical University, No. 117 Nanjing North Street, Shenyang, Liaoning 110002, China
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28
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Klapheke AK, Carvajal-Carmona LG, Cress RD. Racial/ethnic differences in survival among gastric cancer patients in california. Cancer Causes Control 2019; 30:687-696. [PMID: 31102083 DOI: 10.1007/s10552-019-01184-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 05/11/2019] [Indexed: 01/03/2023]
Abstract
BACKGROUND Gastric cancer is an important cause of death among racial/ethnic minorities in the U.S. The objective of this study was to investigate racial disparities in survival among gastric cancer patients within demographic and disease subgroups. METHODS Patients diagnosed with invasive epithelial gastric cancer between 2006 and 2015 were identified from the California Cancer Registry. Cox proportional hazards regression was used to identify factors associated with survival among non-Hispanic whites (NHWs, n = 7,475), non-Hispanic blacks (NHBs, n = 1,246), Hispanics (n = 6,274), and Asians/Pacific Islanders (APIs, n = 4,204). Survival was compared across race/ethnicity within subgroups of demographic and disease factors. Five-year relative survival was also calculated within subgroups. RESULTS There were notable differences in patient characteristics by race/ethnicity, but predictors of survival were similar for each group. Overall, APIs (HR = 0.83, 95% CI: 0.79, 0.88, p < 0.0001) and Hispanics (HR = 0.94, 95% CI: 0.90, 0.99, p = 0.0104) had better survival than NHWs, but NHBs and NHWs did not have different prognosis (HR = 1.06, 95% CI: 0.98, 1.15, p = 0.2237). The survival advantage of APIs persisted in nearly every demographic and disease subgroup, but Hispanics and NHBs had similar survival as NHWs in most groups. Race was not a significant predictor of survival among those with public or no insurance and patients with cardia tumors. CONCLUSIONS There are some differences in survival by race/ethnicity, but race/ethnicity alone cannot explain disparate outcomes in gastric cancer. Future studies, particularly ones that investigate the role of population-specific etiological factors and molecular tumor profiles, are needed to further understand factors associated with survival.
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Affiliation(s)
- Amy K Klapheke
- Public Health Institute, Cancer Registry of Greater California, 1825 Bell St, Ste 102, Sacramento, CA, USA. .,Department of Public Health Sciences, University of California Davis, Davis, CA, USA.
| | - Luis G Carvajal-Carmona
- Population Sciences and Health Disparities Program, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.,Genome Center and Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA
| | - Rosemary D Cress
- Public Health Institute, Cancer Registry of Greater California, 1825 Bell St, Ste 102, Sacramento, CA, USA.,Department of Public Health Sciences, University of California Davis, Davis, CA, USA.,Population Sciences and Health Disparities Program, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA
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