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Wu Z, Wang X, Shi S, Kong D, Ren C, Bian L, Gu Y, An F, Zhan Q, Yan C, Hu C, Chen Y, Jiang R, Chen J. Heterogeneity of T cells regulates tumor immunity mediated by Helicobacter pylori infection in gastric cancer. BMC Cancer 2025; 25:567. [PMID: 40155861 PMCID: PMC11954285 DOI: 10.1186/s12885-025-13957-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 03/17/2025] [Indexed: 04/01/2025] Open
Abstract
The impact of Helicobacter pylori (H. pylori) status on gastric cancer survival remains unclear. In this study, we conducted a prognostic analysis of 488 gastric cancer patients and performed single-cell RNA sequencing (scRNA-seq) on 18,717 T cells from six tumor samples with varying H. pylori statuses. Our findings revealed that gastric cancer patients with H. pylori infection had significantly longer survival times compared to those with negative H. pylori status. After unsupervised re-clustering of T cells based on scRNA-seq data, we identified ten CD4+ and twelve CD8+ clusters. Among them, four CD8+ T cell clusters exhibited distinct distributions based on H. pylori infection status. One cluster, marked by CXCL13, showed high levels of IFNG and GZMB in H. pylori-infected patients, while another cluster, which expressed immune suppression related genes like AREG and PTGER2, was predominantly comprised of cells from non-infected patients. High PTGER2 expression was significantly associated with worse prognosis in patients with high CD8 expression. These insights advance our understanding of H. pylori's influence on T cell responses in gastric cancer, aiding in treatment and prognostic strategies.
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Affiliation(s)
- Zhisheng Wu
- School of Chemistry and Chemical Engineering, Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Medical School, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China
| | - Xinya Wang
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China
| | - Shujing Shi
- Department of Rehabilitation, School of Sport and Health, Nanjing Sport Institute, Nanjing, China
| | - Deyuan Kong
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China
| | - Chuanli Ren
- Department of Laboratory Medicine, Clinical Medical College of Yangzhou University, Yangzhou, China
| | - Lijun Bian
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yuanliang Gu
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Fangmei An
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China
- Department of Gastroenterology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Qiang Zhan
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China
- Department of Gastroenterology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Caiwang Yan
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China
- Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Chupeng Hu
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
| | - Yun Chen
- School of Chemistry and Chemical Engineering, Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Medical School, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China.
- Wuxi People's Hospital, Wuxi People's Hospital of Nanjing Medical University, Wuxi Medical Center, Wuxi, China.
- Department of Immunology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
- Research center for clinical oncology, Jiangsu Cancer Hospital, the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
| | - Runqiu Jiang
- Jiangsu Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China.
| | - Jinfei Chen
- Department of Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
- Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, 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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Xia M, Lei L, Zhao L, Xu W, Zhang H, Li M, Hu J, Cheng R, Hu T. The dynamic oral-gastric microbial axis connects oral and gastric health: current evidence and disputes. NPJ Biofilms Microbiomes 2025; 11:1. [PMID: 39747247 PMCID: PMC11696714 DOI: 10.1038/s41522-024-00623-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 11/25/2024] [Indexed: 01/04/2025] Open
Abstract
Emerging evidence indicates that oral microbes are closely related to gastric microbes and gastric lesions, including gastric atrophy, intestinal metaplasia and gastric cancer (GC). Helicobacter pylori is a key pathogen involved in GC. However, the increasing prevalence of H. pylori-negative GC and gastric dysbiosis in GC patients emphasize the potential role of other microbial factors. In this review, we discussed the current evidence about the relationship between the oral-gastric microbial axis and oral and gastric health. Epidemiologic evidence indicates that poor oral hygiene is related to greater GC risk. Multiple oral-associated microbes are enriched in the stomach of GC patients. Once colonizing the stomach, oral-associated microbes Streptococcus anginosus and Prevotella melaninogenica, are involved in gastric inflammation or carcinogenesis. Microbial metabolites such as lactate, nitrite, and acetaldehyde promote malignant transformation. The stomach, as a checkpoint of microbial transmission in the digestive tract, is of great importance since the link between oral microbes and intestinal diseases has been emphasized. Still, new technologies and standardized metrics are necessary to identify potential pathogenetic microbes for GC and the core microbiota, interactions, richness, colonization, location and effect (CIRCLE). In the future, oral microbes could be candidates for noninvasive indicators to predict gastric diseases.
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Affiliation(s)
- Mengying Xia
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Lei Lei
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
- Department of Microbiology, ADA Forsyth Institute, Cambridge, USA
| | - Linyong Zhao
- Gastric Cancer Center and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Wenqing Xu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
- Faculty of Dentistry, University of Hong Kong, Hong Kong, China
| | - Hongyu Zhang
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Mingming Li
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Jiankun Hu
- Gastric Cancer Center and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Ran Cheng
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
| | - Tao Hu
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Frontier Innovation Center for Dental Medicine Plus & Department of Preventive Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
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Zeng Z, Sun Y, Jiang J, Xu X, Lin H, Li W, Zheng D, Huang Y, Zhao C. Engineered low-pathogenic Helicobacter pylori as orally tumor immunomodulators for the stimulation of systemic immune response. Biomaterials 2024; 311:122672. [PMID: 38897029 DOI: 10.1016/j.biomaterials.2024.122672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 05/14/2024] [Accepted: 06/15/2024] [Indexed: 06/21/2024]
Abstract
Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori (H. pylori) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori. H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori-based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy.
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Affiliation(s)
- Zishan Zeng
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Yue Sun
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Jingwen Jiang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Xiaoyu Xu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Huanxin Lin
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Wanzhen Li
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Dong Zheng
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Yanjuan Huang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China
| | - Chunshun Zhao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China.
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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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Cao Y, Xia H, Tan X, Shi C, Ma Y, Meng D, Zhou M, Lv Z, Wang S, Jin Y. Intratumoural microbiota: a new frontier in cancer development and therapy. Signal Transduct Target Ther 2024; 9:15. [PMID: 38195689 PMCID: PMC10776793 DOI: 10.1038/s41392-023-01693-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 09/20/2023] [Accepted: 10/24/2023] [Indexed: 01/11/2024] Open
Abstract
Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological and pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms, which have been confirmed to be closely related to oncogenesis. The concept of intratumoural microbiota was subsequently proposed. Microbiota could colonise tumour tissues through mucosal destruction, adjacent tissue migration, and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment. Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune destruction, regulating metabolism, and activating invasion and metastasis. Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging, new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination. In addition, interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy, especially immunotherapy, although there are some inevitable challenges. Here, we aim to provide an extensive review of the concept, development history, potential sources, heterogeneity, and carcinogenic mechanisms of intratumoural microorganisms, explore the potential role of microorganisms in tumour prognosis, and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.
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Affiliation(s)
- Yaqi Cao
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Respiratory Diseases of National Health Commission, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
- Hubei Province Engineering Research Center for Tumour-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
- Hubei Province Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Hui Xia
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Respiratory Diseases of National Health Commission, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
- Hubei Province Engineering Research Center for Tumour-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
- Hubei Province Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Xueyun Tan
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Respiratory Diseases of National Health Commission, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
- Hubei Province Engineering Research Center for Tumour-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
- Hubei Province Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Chunwei Shi
- Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Yanling Ma
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Respiratory Diseases of National Health Commission, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Daquan Meng
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Respiratory Diseases of National Health Commission, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Mengmeng Zhou
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Respiratory Diseases of National Health Commission, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Zhilei Lv
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Respiratory Diseases of National Health Commission, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China
| | - Sufei Wang
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Respiratory Diseases of National Health Commission, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
- Hubei Province Engineering Research Center for Tumour-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
- Hubei Province Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
| | - Yang Jin
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Diseases, Key Laboratory of Respiratory Diseases of National Health Commission, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
- Hubei Province Engineering Research Center for Tumour-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
- Hubei Province Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
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7
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Afkhamipour M, Kaviani F, Dalali S, Piri-Gharaghie T, Doosti A. Potential Gastric Cancer Immunotherapy: Stimulating the Immune System with Helicobacter pylori pIRES2-DsRed-Express- ureF DNA Vaccines. Arch Immunol Ther Exp (Warsz) 2024; 72:aite-2024-0004. [PMID: 38346161 DOI: 10.2478/aite-2024-0004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 09/20/2023] [Indexed: 02/15/2024]
Abstract
Most gastric cancers (GC) are thought to be caused by Helicobacter pylori (H. pylori) infections. However, there is mounting evidence that GC patients with positive H. pylori status have improved prognoses. The H. pylori-induced cellular immune reaction may inhibit cancer. In this study, BALB/c mice were immunized using recombinant plasmids that encode the ureF gene of H. pylori. Purified functional splenic CD3+ T lymphocytes are used to study the anticancer effects in vitro and in vivo. The immunological state of GC patients with ongoing H. pylori infection is mimicked by the H. pylori DNA vaccines, which cause a change in the reaction from Th1 to Th2. Human GC cells grow more slowly when stimulated CD3+ T lymphocytes are used as adoptive infusions because they reduce GC xenograft development in vivo. The more excellent ratios of infiltrating CD8+/CD4+ T cells, the decreased invasion of regulatory FOXP3+ Treg lymphocytes, and the increased apoptosis brought on by Caspase9/Caspase-3 overexpression and Survivin downregulation may all contribute to the consequences. Our findings suggest that in people with advanced GC, H. pylori pIRES2-DsRed-Express-ureF DNA vaccines may have immunotherapeutic utility.
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Affiliation(s)
- Mahsa Afkhamipour
- Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Fatemeh Kaviani
- Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Samaneh Dalali
- Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
| | - Tohid Piri-Gharaghie
- Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
- Biotechnology Research Center, East Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Abbas Doosti
- Biotechnology Research Center, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
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8
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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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9
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Nishizuka SS, Nakatochi M, Koizumi Y, Hishida A, Okada R, Kawai S, Sutoh Y, Koeda K, Shimizu A, Naito M, Wakai K. Anti-Helicobacter pylori antibody status is associated with cancer mortality: A longitudinal analysis from the Japanese DAIKO prospective cohort study. PLOS GLOBAL PUBLIC HEALTH 2023; 3:e0001125. [PMID: 36962964 PMCID: PMC10022139 DOI: 10.1371/journal.pgph.0001125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 12/22/2022] [Indexed: 02/10/2023]
Abstract
Paradoxically, patients with advanced stomach cancer who are Helicobacter pylori-positive (HP+) have a higher survival rate than those who are HP-. This finding suggests that HP infection has beneficial effects for cancer treatment. The present study examines whether HP+ individuals have a lower likelihood of death from cancer than those who are HP-. Prospective cohort data (n = 4,982 subjects enrolled in the DAIKO study between 2008-2010) were used to assess whether anti-HP antibody status was associated with cancer incidence. The median age in the primary registry was 53 years-old (range 35-69 years-old). Over the 8-year observation period there were 234 (4.7%) cancer cases in the cohort and 88 (1.8%) all-cause deaths. Urine anti-HP antibody data was available for all but one participant (n = 4,981; 99.98%). The number of HP+ and HP- individuals was 1,825 (37%) and 3,156 (63%), respectively. Anti-HP antibody distribution per birth year revealed that earlier birth year was associated with higher HP+ rates. With a birth year-matched cohort (n = 3,376), all-cancer incidence was significantly higher in HP+ individuals than those who were HP- (p = 0.00328), whereas there was no significant difference in the cancer death rate between HP+ and HP- individuals (p = 0.888). Cox regression analysis for prognostic factors revealed that the hazards ratio of HP+ was 1.59-fold (95%CI 1.17-2.26) higher than HP- in all-cancer incidence. Potential systemic effects of HP+ status may contribute to reduced likelihood of death for patients after an initial diagnosis of cancer.
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Affiliation(s)
- Satoshi S Nishizuka
- Division of Biomedical Research & Development, Iwate Medical University Institute for Biomedical Sciences, Yahaba, Japan
| | - Masahiro Nakatochi
- Department of Integrated Health Sciences, Public Health Informatics Unit, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuka Koizumi
- Division of Biomedical Research & Development, Iwate Medical University Institute for Biomedical Sciences, Yahaba, Japan
| | - Asahi Hishida
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Rieko Okada
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Sayo Kawai
- Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
| | - Yoichi Sutoh
- Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Yahaba, Japan
| | - Keisuke Koeda
- Department of Medical Safety Science, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Atsushi Shimizu
- Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Yahaba, Japan
- Division of Biomedical Information Analysis, Iwate Medical University Institute for Biomedical Sciences, Yahaba, Japan
| | - Mariko Naito
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Department of Oral Epidemiology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan
| | - Kenji Wakai
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
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10
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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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11
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Sun QH, Zhang J, Shi YY, Zhang J, Fu WW, Ding SG. Microbiome changes in the gastric mucosa and gastric juice in different histological stages of Helicobacter pylori-negative gastric cancers. World J Gastroenterol 2022; 28:365-380. [PMID: 35110955 PMCID: PMC8771614 DOI: 10.3748/wjg.v28.i3.365] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 12/14/2021] [Accepted: 01/10/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The gastric microbiota in patients with gastric cancer (GC) has received increasing attention, but the profiling of the gastric microbiome through the histological stages of gastric tumorigenesis remains poorly understood, especially for patients with Helicobacter pylori-negative GC (HPNGC).
AIM To characterize microbial profiles of gastric mucosa and juice for HPNGC carcinogenesis and identify distinct taxa in precancerous lesions.
METHODS The 16S rRNA gene analysis was performed on gastric mucosa from 134 Helicobacter pylori-negative cases, including 56 superficial gastritis (SG), 9 atrophic gastritis (AG), 27 intestinal metaplasia (IM), 29 dysplasia (Dys), and 13 GC cases, to investigate differences in gastric microbial diversity and composition across the disease stages. In addition, paired gastric mucosa and juice samples from 18 SG, 18 IM, and 18 Dys samples were analyzed. α-Diversity was measured by Shannon and Chao1 indexes, and β-diversity was calculated using partial least squares discrimination analysis (PLS-DA). Differences in the microbial composition across disease stages in different sample types were assessed using the linear discriminant analysis effect size.
RESULTS The diversity and composition of the bacterial microbiota in the gastric mucosa changed progressively across stages of gastric carcinogenesis. The diversity of the gastric mucosa microbiota was found to be significantly lower in the IM and Dys groups than in the SG group, and the patients with GC had the lowest bacterial community richness (P < 0.05). Patients with IM and those with Dys had similar gastric mucosa microbiota profiles with Ralstonia and Rhodococcus as the predominant genera. Microbial network analysis showed that there was increasing correlation strength between IM and Dys (|correlation threshold|≥ 0.5, P < 0.05). GC and its precancerous lesions have distinguishable bacterial taxa; our results identified HPNGC-associated bacteria Streptococcaceae and Lactobacillaceae (P < 0.05). Additionally, across precancerous lesion stages from AG to Dys in Helicobacter pylori-negative patients, Burkholderiaceae abundance continuously increased, while Streptococcaceae and Prevotellaceae abundance presented a continuous downward trend. Furthermore, the microbial diversity was higher in gastric juice (P < 0.001) than in the mucosa, while PLS-DA revealed a statistically significant difference between the two groups (ANOSIM, P = 0.001). A significant difference in the microbial structure was identified, with Proteobacteria being more prevalent in the gastric mucosa and Firmicutes being more abundant in gastric juice.
CONCLUSION Our results provide insights into potential taxonomic biomarkers for HPNGC and its precancerous stages and assist in predicting the prognosis of IM and Dys based on the mucosal microbiota profile.
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Affiliation(s)
- Qing-Hua Sun
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Jing Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Yan-Yan Shi
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 10019, China
| | - Jing Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Wei-Wei Fu
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
| | - Shi-Gang Ding
- Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China
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12
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Relationship of prognostic factors in stomach cancer with Helicobacter pylori: A retrospective study. Acta Gastroenterol Belg 2022; 85:35-45. [PMID: 35304992 DOI: 10.51821/85.1.7352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Background and study aims The prognostic value of H. pylori, which infects more than half of the human population living in the world and plays a role in gastric cancer pathogenesis, is controversial. Our aim is to investigate the relationship between H. pylori and prognostic factors in gastric cancer. Patients and methods The data of 110 patients (38 females and 72 males) that underwent surgeries due to gastric cancer between 2014 and 2017 were retrospectively analyzed. The relationships between survival (disease-free and overall) and factors such as p53, HER2/neu, Ki-67, neutrophil and platelet lymphocyte ratio (NLR / PLR), histopathological and demographic characteristics were examined. In addition, the results of H. pylori positive and negative groups were compared. Results Sixty-one (55%) patients were H. pylori negative and 49 (45%) were positive. In multivariate analysis, TNM stage, lymph node capsule invasion and NLR were determined as independent prognostic factors in both disease-free and overall survival. Age>62 and PLR>14.3 were determined as independent predictive factors of poor prognosis in overall survival. In univariate analysis, tumor diameter of >4.3 cm, lymphovascular and perineural invasion, and diffuse p53 expression were determined as predictive factors of poor prognosis in disease-free and overall survival. The effectiveness of these markers in prognosis was not different between H. pylori negative and positive groups. Conclusion While age, tumor diameter, TNM stage, lymph node capsule invasion, perineural and lymphovascular invasion, diffuse p53, PLR, and NLR were determined as prognostic factors in gastric cancer, these factors were not affected by the presence of H. pylori.
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13
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Morais S, Peleteiro B, Araújo N, Malekzadeh R, Ye W, Plymoth A, Tsugane S, Hidaka A, Shigueaki Hamada G, López-Carrillo L, Zaridze D, Maximovich D, Aragonés N, Castaño-Vinyals G, Pakseresht M, Hernández-Ramírez RU, López-Cervantes M, Leja M, Gasenko E, Pourfarzi F, Zhang ZF, Yu GP, Derakhshan MH, Pelucchi C, Negri E, La Vecchia C, Lunet N. Identifying the profile of Helicobacter pylori negative gastric cancers: a case only analysis within the Stomach cancer Pooling (StoP) Project. Cancer Epidemiol Biomarkers Prev 2021; 31:200-209. [PMID: 34728467 DOI: 10.1158/1055-9965.epi-21-0402] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 06/25/2021] [Accepted: 10/22/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The prevalence of Helicobacter pylori negative gastric cancer (HpNGC) can be as low as 1%, when infection is assessed using more sensitive tests or considering the presence of gastric atrophy. HpNGC may share a high-risk profile contributing to the occurrence of cancer in the absence of infection. We estimated the proportion of HpNGC, using different criteria to define infection status, and compared HpNGC and positive cases regarding gastric cancer risk factors. METHODS Cases from 12 studies from the Stomach cancer Pooling (StoP) Project providing data on H. pylori infection status determined by serological test were included. HpNGC was reclassified as positive (eight studies) when cases presented CagA markers (four studies), gastric atrophy (six studies), or advanced stage at diagnosis (three studies), and were compared with positive cases. A two-stage approach (random-effects models) was used to pool study-specific prevalence and adjusted odds ratios (ORs). RESULTS Among non-cardia cases, the pooled prevalence of HpNGC was 22.4% (n=166/853) and decreased to 7.0% (n=55) when considering CagA status; estimates for all criteria were 21.8% (n=276/1325) and 6.6% (n=97), respectively. HpNGC had a family history of gastric cancer more often (OR=2.18, 95% confidence interval [CI]:1.03-4.61) and were current smokers (OR=2.16, 95%CI:0.52-9.02). CONCLUSION This study found a low prevalence of HpNGC, who are more likely to have a family history of gastric cancer in first-degree relatives. IMPACT Our results support that H. pylori infection is present in most non-cardia gastric cancers, and suggest that HpNGC may have distinct patterns of exposure to other risk factors.
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Affiliation(s)
- Samantha Morais
- Department of Clinical Epidemiology, Predictive Medicine and Public Health, Instituto de Saúde Pública da Universidade do Porto
| | - Bárbara Peleteiro
- Department of Hygiene and Epidemiology, University of Porto Medical School
| | - Natália Araújo
- Department of Clinical Epidemiology, Predictive Medicine and Public Health, Instituto de Saúde Pública da Universidade do Porto
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Tehran University of Medical Sciences
| | - Weimin Ye
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute
| | - Amelie Plymoth
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Centre
| | | | | | | | - David Zaridze
- Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Center
| | - Dmitry Maximovich
- Department of Epidemiology and Prevention, Russian N.N. Blokhin Cancer Research Center
| | | | - Gemma Castaño-Vinyals
- Non-communicable Diseases and Environment, Center for Research in Environmental Epidemiology
| | - Mohammadreza Pakseresht
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences
| | | | | | - Marcis Leja
- Riga Eastern Clinical University hospital, Digestive Diseases Centre GASTRO, University of Latvia
| | - Evita Gasenko
- Riga Eastern Clinical University hospital, Digestive Diseases Centre GASTRO, University of Latvia
| | - Farhad Pourfarzi
- Digestive Disease Research Center, Ardabil University of Medical Sciences
| | - Zuo-Feng Zhang
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles
| | - Guo-Pei Yu
- Medical Informatics Center, Peking University
| | | | - Claudio Pelucchi
- Department of Clinical Sciences and Community Health, University of Milan
| | - Eva Negri
- Epidemiology, Istituto di Ricerche Farmacologiche Mario Negri
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan
| | - Nuno Lunet
- Departamento de Ciências da Saúde Pública e Forenses e Educação Médica, Faculdade de Medicina, Universidade do Porto
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14
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Relationship of prognostic factors in stomach cancer with helicobacter pylori: a retrospective study. Acta Gastroenterol Belg 2021; 84:607-617. [PMID: 34965043 DOI: 10.51821/84.4.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND STUDY AIMS The prognostic value of H. pylori, which infects more than half of the human population living in the world and plays a role in gastric cancer pathogenesis, is controversial. Our aim is to investigate the relationship between H. pylori and prognostic factors in gastric cancer. PATIENTS AND METHODS The data of 110 patients (38 females and 72 males) that underwent surgeries due to gastric cancer between 2014 and 2017 were retrospectively analyzed. The relationships between survival (disease-free and overall) and factors such as p53, HER2/neu, Ki-67, neutrophil and platelet lymphocyte ratio (NLR / PLR), histopathological and demographic characteristics were examined. In addition, the results of H. pylori positive and negative groups were compared. RESULTS Sixty-one (55%) patients were H. pylori negative and 49 (45%) were positive. In multivariate analysis, TNM stage, lymph node capsule invasion and NLR were determined as independent prognostic factors in both disease-free and overall survival. Age>62 and PLR>14.3 were determined as independent predictive factors of poor prognosis in overall survival. In univariate analysis, tumor diameter of >4.3 cm, lymphovascular and perineural invasion, and diffuse p53 expression were determined as predictive factors of poor prognosis in disease-free and overall survival. The effectiveness of these markers in prognosis was not different between H. pylori negative and positive groups. CONCLUSION While age, tumor diameter, TNM stage, lymph node capsule invasion, perineural and lymphovascular invasion, diffuse p53, PLR, and NLR were determined as prognostic factors in gastric cancer, these factors were not affected by the presence of H. pylori.
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15
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Yu P, Wang Y, Yu Y, Wang A, Huang L, Zhang Y, Liu W, Wu H, Yao M, Du YA, Cheng X. Deep Targeted Sequencing and Its Potential Implication for Cancer Therapy in Chinese Patients with Gastric Adenocarcinoma. Oncologist 2021; 26:e756-e768. [PMID: 33511732 PMCID: PMC8100567 DOI: 10.1002/onco.13695] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 12/30/2020] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Gastric cancer (GC) has a high incidence and mortality rate, especially in East Asians, and about 90% of GCs are adenocarcinomas. Histological and etiological heterogeneity and ethnic diversity make molecular subtyping of GC complicated, thus making it difficult to determine molecular division systems and standard treatment modalities. Limited cohorts from South Korea, Singapore, Australia, and Japan have been studied; however, the mutational landscape of gastric adenocarcinomas in Chinese patients is still unknown. METHODS We performed a targeted sequencing panel focusing on cancer-related genes and tumor-associated microorganisms of 529 gastric adenocarcinoma samples with matched blood controls. We identified 449 clinically relevant gene mutations. RESULTS Approximately 47.1% of Chinese patients with GC harbored at least one actionable mutation. The top somatic mutations were TP53, ARID1A, LRP1B, PIK3CA, ERBB2, CDH1, KRAS, FAT4, CCNE1, and KMT2D. Truncation mutations of ARID1A, KMT2D, RNF43, TGFBR2, and CIC occurred in patients with high tumor mutational burden. Gene amplifications of ERBB2, CCNE1, CDK12, and CCND1 were detected in patients with low tumor mutational burden. Pathway analysis revealed common gene alterations in the Wnt and PI3K/Akt signaling pathways. The ratio of patients with high microsatellite instability was significantly lower than other cohorts, and high microsatellite instability and Epstein-Barr virus (EBV)-positive features seemed mutually inclusive in Chinese patients with GC. In 44 (8.3%) patients, 45 germline mutations were identified, among which SPINK1 mutations, all SPINK1 c.194 + 2T > C, were present in 15.9% (7/44) of patients. Microorganisms found in Chinese patients with GC included Helicobacter pylori, EBV, hepatitis B virus, and human papillomavirus types 16 and 18. CONCLUSION Identification of varied molecular features by targeted next-generation sequencing provides more insight into patient stratification and offers more possibilities for both targeted therapies and immunotherapies of Chinese patients with GC. IMPLICATIONS FOR PRACTICE This study investigated the genomic alteration profile of 529 Chinese patients with gastric adenocarcinoma by deep targeting sequencing, which might be the largest Chinese cohort on the genomic research of gastric adenocarcinoma up to now.
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Affiliation(s)
- Pengfei Yu
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China
| | - Yusheng Wang
- Digestion Department, Shanxi Provincial Cancer Hospital, Taiyuan, People's Republic of China
| | - Yanfei Yu
- OrigiMed Inc., Shanghai, People's Republic of China
| | - Aodi Wang
- OrigiMed Inc., Shanghai, People's Republic of China
| | - Ling Huang
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China
| | - Yuan Zhang
- OrigiMed Inc., Shanghai, People's Republic of China
| | - Wenjing Liu
- OrigiMed Inc., Shanghai, People's Republic of China
| | - Haiyan Wu
- OrigiMed Inc., Shanghai, People's Republic of China
| | - Ming Yao
- OrigiMed Inc., Shanghai, People's Republic of China
| | - Yi-An Du
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China
| | - Xiangdong Cheng
- Department of Gastric Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, People's Republic of China
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Effect of Helicobacter pylori eradication after subtotal gastrectomy on the survival rate of patients with gastric cancer: follow-up for up to 15 years. Gastric Cancer 2020; 23:1051-1063. [PMID: 32361784 DOI: 10.1007/s10120-020-01076-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 04/21/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Helicobacter pylori (HP) is known to play an important role in the development of gastric cancer (GC). The aim of this study was to analyze the effect of HP eradication on the survival rate and cancer recurrence in patients who underwent subtotal gastrectomy for GC. DESIGN Totally 1,031 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital from 2003 to 2017 and positive for HP infection were analyzed. The overall and GC-related survival according to HP eradication were compared; risk factors for GC-specific death and cancer recurrence were analyzed, and propensity score matching (PSM) was performed. RESULTS Statistically significant benefits of overall and GC-specific survival were observed in the eradicated group compared to the non-eradicated group (P < 0.001), and these benefits were maintained after PSM (P < 0.001) in both of early and advance stage. In Cox proportional hazards multivariate analyses, cancer stage (stage II, adjusted hazard ratio [aHR] = 9.33, P < 0.001; stage III or IV, aHR = 26.17, P < 0.001), and HP positivity (aHR = 3.41, P = 0.001) were independent risk factors for GC-specific death; cancer stage (cancer stage II, aHR = 7.08, P < 0.001; cancer stage III or IV, aHR = 19.64, P < 0.001) and HP positivity (aHR = 2.70; P = 0.005) were independent risk factors for cancer recurrence. CONCLUSION Our results suggest that HP needed to be conducted more intensively in patients who are surgically treated for GC, regardless of cancer stage.
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17
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What are the effects of IL-1β (rs1143634), IL-17A promoter (rs2275913) and TLR4 (rs4986790) gene polymorphism on the outcomes of infection with H. pylori within as Iranian population; A systematic review and meta-analysis. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100735] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Nguyen TH, Mallepally N, Hammad T, Liu Y, Thrift AP, El-Serag HB, Tan MC. Prevalence of Helicobacter pylori Positive Non-cardia Gastric Adenocarcinoma Is Low and Decreasing in a US Population. Dig Dis Sci 2020; 65:2403-2411. [PMID: 31728790 PMCID: PMC7220821 DOI: 10.1007/s10620-019-05955-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 11/09/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND Helicobacter pylori infection is an established causal factor for non-cardia gastric cancer. H. pylori negative gastric cancer prevalence among US patients is unclear. METHODS This retrospective cohort study examined H. pylori prevalence among consecutive patients with incident non-cardia gastric adenocarcinoma at the Houston VA Hospital (11/2007-10/2018). H. pylori positivity was defined by H. pylori on histopathology, positive antibody serology, stool antigen, or urea breath testing. We examined for trends in H. pylori negative gastric cancer based on year of diagnosis. Associations between histopathologic and cancer-related outcomes with H. pylori positivity were determined using regression models. RESULTS Of 91 patients with gastric adenocarcinoma, most were men (N = 87, 95.6%), black (N = 47, 51.6%), with mean age at diagnosis of 68.0 years (SD 10.8). In addition to gastric cancer biopsy histopathology, 74 patients (81.3%) had ≥ 1 testing for H. pylori, including antibody serology (n = 34), non-cancer gastric biopsy histopathology (n = 63), or stool antigen (n = 1). The overall prevalence of H. pylori infection was 38.5% and 45.9% among patients with ≥ 2 H. pylori tests. The proportions of H. pylori positive gastric cancer decreased from 50.0% (2007-2010) to 43.4% (2011-2014) and 29.3% (2015-2018) (p = 0.096). Active/acute gastritis (adjOR 3.74), atrophic gastritis (adjOR 15.30), and gastric intestinal metaplasia (adjOR 3.65) were associated with H. pylori positive gastric cancer. DISCUSSION The prevalence of H. pylori infection among patients with non-cardia gastric adenocarcinoma is relatively low (38.5-45.9%) and decreasing over time. This finding suggests there may be other important causal factors apart from H. pylori for gastric adenocarcinoma.
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Affiliation(s)
- Theresa H Nguyen
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, 77030-3498, USA
| | - Niharika Mallepally
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, 77030-3498, USA
| | - Tariq Hammad
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, 77030-3498, USA
| | - Yan Liu
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, 77030-3498, USA
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
- Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, 77030-3498, USA
- Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA
| | - Mimi C Tan
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, MS: BCM 285, Houston, TX, 77030-3498, USA.
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Liu C, Hu C, Li Z, Feng J, Huang J, Yang B, Wen T. Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance. Cancer Cell Int 2020; 20:279. [PMID: 32617077 PMCID: PMC7325377 DOI: 10.1186/s12935-020-01368-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Accepted: 06/19/2020] [Indexed: 12/11/2022] Open
Abstract
Background Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in Helicobacter pylori-negative gastric cancer (HP− GC). Methods The clinical, gene expression profile data and AS events of 138 HP− GC patients were obtained from the database named the cancer genome atlas. Differently expressed AS (DEAS) events were determined by a comparison of the PSI values between HP− GC samples and adjacent normal samples. Unsupervised clustering analysis, proportional regression and Kaplan–Meier analysis were used to explore the association between clinical data and immune features and to establish two nomograms about the prognosis of HP− GC. Finally, splicing networks were constructed using Cytoscape. Results A total of 48141 AS events and 1041 DEAS events were found in HP− GC. Various functions and pathways of DEAS events parent genes were enriched, such as cell-substrate junction, cell leading edge, focal adhension, and AMPK signaling. Seven overall survival (OS)-related and seven disease-free survival (DFS)-related AS events were used to construct the prognostic signatures. Based on the independent prognostic factors, two nomograms were established and showed excellent performance. Then, splicing regulatory networks among the correlations suggested that splicing factors were significantly associated with prognostic DEASs. Finally, the unsupervised clustering analysis revealed that DEAS-based clusters were associated with clinical characteristics, tumor microenvironment, tumor mutation burden, and immune features. Conclusion Seven OS-related and seven DFS-related AS events have been found to be correlated with the prognosis of HP− GC and can be used as prognostic factors to establish an effective nomogram.
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Affiliation(s)
- Chuan Liu
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001 Liaoning China.,Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, 110001 Liaoning China
| | - Chuan Hu
- Qingdao University Medical College, Qingdao, 266071 Shandong China
| | - Zhi Li
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001 Liaoning China.,Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, 110001 Liaoning China
| | - Jing Feng
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001 Liaoning China.,Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, 110001 Liaoning China
| | - Jiale Huang
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001 Liaoning China.,Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, 110001 Liaoning China
| | - Bowen Yang
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001 Liaoning China.,Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, 110001 Liaoning China
| | - Ti Wen
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, 110001 Liaoning China.,Liaoning Province Clinical Research Center for Cancer, Shenyang, 110001 Liaoning China.,Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, 110001 Liaoning China
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20
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Huang L, Chen L, Gui ZX, Liu S, Wei ZJ, Xu AM. Preventable lifestyle and eating habits associated with gastric adenocarcinoma: A case-control study. J Cancer 2020; 11:1231-1239. [PMID: 31956369 PMCID: PMC6959061 DOI: 10.7150/jca.39023] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 11/14/2019] [Indexed: 01/19/2023] Open
Abstract
Background: Besides the well-established risk factors for gastric adenocarcinoma (GaC), many other etiological factors remain largely unexplored. This large comprehensive case-control study aimed to investigate the preventable lifestyle and eating habits associated with GaC. Methods: Consecutive patients with primary microscopically-confirmed GaC diagnosed in 2016-2018 were matched by sex, age, height, and socioeconomic status at a 1:1 ratio with healthy controls. Association of GaC versus control with investigated factors was assessed using the multivariable-adjusted conditional logistic regression for paired samples. Results: Together 302 GaC patients and 302 healthy controls were investigated. Participants receiving higher education and those eating majorly vegetables had less frequently GaC. The majorly frying cooking habit was associated with a higher incidence of GaC. People complaining about poor sleep quality had more often GaC. The more often one smoked, the more often he/she had GaC. A higher frequency for having pickled food was associated with more frequent GaC, while having more frequently vegetables/fruit, beans, or kelps was associated with less often GaC. A greater preference for sour or bitter taste was associated with less frequent GaC. The frequencies of thin liquid intake after meal, swallowing hot food without adequate cooling, doing other things while eating, eating overnight food, and eating midnight snack were all positively associated with GaC, while going to bed regularly was associated with less often GaC. Conclusions: Education level, sleep quality, smoking, the frequencies of use of several foods and seasonings, the preference for specific tastes, and various eating and living habits were associated with GaC. The findings offer important hints for further prospective investigations and for easy effective GaC-preventative strategy-making.
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Affiliation(s)
- Lei Huang
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University
| | - Lei Chen
- Second Clinical Medicine College of Anhui Medical University
| | - Zhong-Xuan Gui
- Second Clinical Medicine College of Anhui Medical University
| | - Shun Liu
- Second Clinical Medicine College of Anhui Medical University
| | - Zhi-Jian Wei
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University
| | - A-Man Xu
- Department of General Surgery, the First Affiliated Hospital of Anhui Medical University
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Dorosti S, Jafarzadeh Ghoushchi S, Sobhrakhshankhah E, Ahmadi M, Sharifi A. Application of gene expression programming and sensitivity analyses in analyzing effective parameters in gastric cancer tumor size and location. Soft comput 2019. [DOI: 10.1007/s00500-019-04507-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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22
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Cheng Y, Xiao Y, Zhou R, Liao Y, Zhou J, Ma X. Prognostic significance of helicobacter pylori-infection in gastric diffuse large B-cell lymphoma. BMC Cancer 2019; 19:842. [PMID: 31455250 PMCID: PMC6712724 DOI: 10.1186/s12885-019-6067-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 08/20/2019] [Indexed: 02/06/2023] Open
Abstract
Background Helicobacter pylori (H. pylori) is thought to have an oncogenic effect on the development of gastric malignancies. However, the effect of H. pylori status on the prognosis of gastric diffuse large B-cell lymphoma (DLBCL) remains unconfirmed. This study aimed to identify the prognostic importance of H. pylori infection in de novo gastric DLBCL. Methods One hundred and twenty-nine patients diagnosed with primary de novo gastric DLBCL at the West China Hospital of Sichuan University from 1st January 2009 to 31st May 2016 were included. The clinical features of the patients were documented. H. pylori status was assessed via urease breath tests and histologic examinations. The prognostic value of H. pylori was verified via univariate and multivariate analyses. Results Over a median follow-up of 52.2 months (range 4–116), the 5-year overall survival (OS) for all patients was 78.7%. Patients with H. pylori infections had significantly better 5-year PFS and OS than did the H. pylori-negative subgroup (5-year PFS, 89.3% vs. 74.1%, P = 0.040; 5-year OS, 89.7% vs. 71.8%, P = 0.033). Negative H. pylori status and poor ECOG performance were independent negative prognostic indicators for both PFS and OS (PFS, P = 0.045 and P = 0.001, respectively; OS, P = 0.021 and P < 0.001, respectively). Conclusions H. pylori status in de novo gastric DLBCL can be a promising predictor of disease outcome, and patients with negative H. pylori status require careful follow-up since they tend to have a worse outlook.
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Affiliation(s)
- Yuan Cheng
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China
| | - Yinan Xiao
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China
| | - Ruofan Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China
| | - Yi Liao
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China
| | - Jing Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China
| | - Xuelei Ma
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People's Republic of China.
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Kono Y, Kanzaki H, Tsuzuki T, Takatani M, Nasu J, Kawai D, Takenaka R, Tanaka T, Iwamuro M, Kawano S, Kawahara Y, Fujiwara T, Okada H. A multicenter observational study on the clinicopathological features of gastric cancer in young patients. J Gastroenterol 2019; 54:419-426. [PMID: 30374622 DOI: 10.1007/s00535-018-1525-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Accepted: 10/23/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND The details of gastric cancer in young patients remain unclear because of the low prevalence of the disease. This study aimed to clarify the clinicopathological features and prognosis of gastric cancer in young patients. METHODS From January 2007 to January 2016, patients in their 20s and 30s who were diagnosed with primary gastric cancer at 4 hospitals were enrolled. Their clinical characteristics and prognosis were evaluated. RESULTS The total number of patients was 72. The median age was 36 years, and the ratio of males to females was 1:1. The dominant histological type was undifferentiated type (66/72, 92%). Helicobacter pylori (H. pylori) was positive in 81% (54/67). Although there were some asymptomatic patients in stages I-III, all stage IV patients had some clinical symptoms at the diagnosis. The percentage of stage IV was significantly higher in patients in their 20s than in those in their 30s (75% vs. 25%, P < 0.001). The Kaplan-Meier method showed that the overall survival of patients in their 20s was significantly lower than that of patients in their 30s (P = 0.037). CONCLUSIONS A high rate of H. pylori infection was revealed in young gastric cancer patients. The patients in their 20s had a worse prognosis than those in their 30s. We should consider examining the H. pylori infection status for young patients as well as older patients to identify high-risk populations.
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Affiliation(s)
- Yoshiyasu Kono
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
| | - Hiromitsu Kanzaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Takao Tsuzuki
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Masahiro Takatani
- Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Japan
| | - Junichirou Nasu
- Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Daisuke Kawai
- Department of Internal Medicine, Tsuyama Chuo Hospital, Tsuyama, Japan
| | - Ryuta Takenaka
- Department of Internal Medicine, Tsuyama Chuo Hospital, Tsuyama, Japan
| | - Takehiro Tanaka
- Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Masaya Iwamuro
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Seiji Kawano
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Yoshiro Kawahara
- Department of Endoscopy, Okayama University Hospital, Okayama, Japan
| | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
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Li G, Yu S, Xu J, Zhang X, Ye J, Wang Z, He Y. The prognostic role of Helicobacter pylori in gastric cancer patients: A meta-analysis. Clin Res Hepatol Gastroenterol 2019; 43:216-224. [PMID: 30361060 DOI: 10.1016/j.clinre.2018.08.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 07/04/2018] [Accepted: 08/21/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND The prognostic value of Helicobacter pylori (H. pylori) infection in gastric cancer patients has been investigated over many years; however, the results remain inconclusive. Thus, we performed a comprehensive review of currently available evidence via a systemic meta-analysis to evaluate the effects of H. pylori infection on the prognosis of gastric cancer patients. METHODS Studies that evaluated the prognostic value of H. pylori infection in gastric cancer were extracted in March 2016 by searching PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We obtained or calculated hazard ratios (HRs) and the associated 95% confidence intervals (CIs) from the identified studies, and conducted random-effects model analyses of overall survival and progression-free survival. Twenty-four studies with a cumulative sample size of 7191 patients were included in our analysis. RESULTS Our meta-analysis revealed that H. pylori infection is an indicator of improved overall survival in gastric cancer patients (HR, 0.79; 95% CI, 0.64-0.99); however, this was only true for European patients. The benefits of H. pylori infection were not detected in Asian gastric cancer patients (HR, 1.01; 95% CI, 0.91-1.12) or those in the United States (HR, 0.88; 95% CI, 0.73-1.05). Subgroup analyses revealed that the prognostic significance of H. pylori infection differed with respect to the year of study publication, number of patients, H. pylori detection method, tumor stage, H. pylori-positive rate, and risk of bias. The prognostic value of H. pylori infection on progression-free survival was unclear (HR, 0.84; 95% CI, 0.70-1.01). CONCLUSIONS These data provide limited, moderate-quality evidence that H. pylori infection is an indicator of good prognosis in European gastric cancer patients. However, this is not necessarily true for other populations.
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Affiliation(s)
- Guanghua Li
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun-Yat-sen University, No. 58, Zhongshan 2nd street, 510080 Guangzhou, Guangdong, PR China.
| | - Shuangjin Yu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun-Yat-sen University, No. 58, Zhongshan 2nd street, 510080 Guangzhou, Guangdong, PR China
| | - Jianbo Xu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun-Yat-sen University, No. 58, Zhongshan 2nd street, 510080 Guangzhou, Guangdong, PR China
| | - Xinhua Zhang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun-Yat-sen University, No. 58, Zhongshan 2nd street, 510080 Guangzhou, Guangdong, PR China
| | - Jinning Ye
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun-Yat-sen University, No. 58, Zhongshan 2nd street, 510080 Guangzhou, Guangdong, PR China.
| | - Zhao Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun-Yat-sen University, No. 58, Zhongshan 2nd street, 510080 Guangzhou, Guangdong, PR China.
| | - Yulong He
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun-Yat-sen University, No. 58, Zhongshan 2nd street, 510080 Guangzhou, Guangdong, PR China.
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Lv Z, Zhao L, Jin W. Protein changes in gastric epithelial cells RGM-1 in response to Helicobacter pylori infection. J Cell Biochem 2019; 120:3197-3202. [PMID: 30582187 DOI: 10.1002/jcb.27585] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 08/07/2018] [Indexed: 12/13/2022]
Abstract
Helicobacter pylori-induced inflammation significantly increases the risk of gastric cancer. To investigate the role of H. pylori infection in gastric epithelial cell carcinogenesis, flow cytometry was used to analyze the apoptosis of gastric epithelial cells infected by H. pylori. Next, LTQ MS mass spectrometry (MS) was applied to identify protein changes in gastric epithelial cells infected with H. pylori, and then bioinformatics was adopted to analyze the cellular localization and biological function of differential proteins. LTQ MS/MS successfully identified identified 22 differential proteins successfully, including 20 host-cell proteins and two H. pylori bacterial proteins. Also, human proteins were located in all areas of cells and involved in various cell biological functions. The oncogene proteins p53, p16, and C-erbB-2 proteins in H. pylori-infected RGM-1 cells were remarkably increased from the analysis by Western blot analysis. H. pylori infection of gastric epithelial cells leads to changes in various protein components in the cell, and enhances the expression of oncogene proteins, thereby increasing the possibility of possibility of carcinogenesis of H. pylori infection.
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Affiliation(s)
- Zengfa Lv
- General Surgery Department, Hanzhong Central Hospital, Hanzhong City, Shaanxi, China
| | - Lizhi Zhao
- General Surgery Department, Hanzhong Central Hospital, Hanzhong City, Shaanxi, China
| | - Weimin Jin
- Gastroenterology Department, Hanzhong Central Hospital, Hanzhong City, Shaanxi, China
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Xue LJ, Mao XB, Liu XB, Gao H, Chen YN, Dai TT, Shao SW, Chen HM, Chu XY. Activation of CD3 + T cells by Helicobacter pylori DNA vaccines in potential immunotherapy of gastric carcinoma. Cancer Biol Ther 2019; 20:866-876. [PMID: 30786815 DOI: 10.1080/15384047.2019.1579957] [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] [Indexed: 01/13/2023] Open
Abstract
Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3+ T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3+ T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3+ T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8+/CD4+ T cells, reduced infiltration of regulatory FOXP3+ T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3+ T cells in those with advanced GC.
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Affiliation(s)
- Li-Jun Xue
- a Department of Oncology , Jinling Hospital, Nanjing University Clinical School of Medicine , Nanjing , China.,b State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Xiao-Bei Mao
- a Department of Oncology , Jinling Hospital, Nanjing University Clinical School of Medicine , Nanjing , China
| | - Xiao-Bei Liu
- a Department of Oncology , Jinling Hospital, Nanjing University Clinical School of Medicine , Nanjing , China
| | - Han Gao
- c Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences , Chinese Academy of Science , Shanghai , China
| | - Ya-Nan Chen
- a Department of Oncology , Jinling Hospital, Nanjing University Clinical School of Medicine , Nanjing , China
| | - Ting-Ting Dai
- a Department of Oncology , Jinling Hospital, Nanjing University Clinical School of Medicine , Nanjing , China
| | - Sheng-Wen Shao
- d Laboratory of Innovation , Medical School of Huzhou Teachers College , Huzhou , China
| | - Hong-Min Chen
- b State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health , Xiamen University , Xiamen , China
| | - Xiao-Yuan Chu
- a Department of Oncology , Jinling Hospital, Nanjing University Clinical School of Medicine , Nanjing , China
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27
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Fang WL, Huang KH, Chang SC, Lin CH, Chen MH, Chao Y, Lo SS, Li AFY, Wu CW, Shyr YM. Comparison of the Clinicopathological Characteristics and Genetic Alterations Between Patients with Gastric Cancer with or Without Helicobacter pylori Infection. Oncologist 2019; 24:e845-e853. [PMID: 30796154 DOI: 10.1634/theoncologist.2018-0742] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 01/14/2019] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Helicobacter pylori (HP) can induce epithelial cells and intestinal metaplasia with genetic damage that makes them highly susceptible to the development of gastric cancer (GC). MATERIALS AND METHODS Between 2005 and 2010, 356 patients with gastric cancer who received curative surgery were enrolled. Analysis of HP, Epstein-Barr virus (EBV) infection, PIK3CA amplification, and mutation analysis of 68 mutations in eight genes using a mass spectrometric single-nucleotide polymorphism genotyping technology was conducted. The clinicopathological characteristics of patients with or without HP infection were compared. RESULTS Among the 356 patients, 185 (52.0%) had HP infection. For intestinal-type GC, patients with HP infection were more likely to be younger and had fewer PI3K/AKT pathway genetic mutations than those without HP infection. For diffuse-type GC, patients with HP infection were characterized by less male predominance, less lymphoid stroma, fewer microsatellite instability-high tumors, and fewer PI3K/AKT pathway genetic mutations than those without HP infection. Patients with HP infection had less tumor recurrence and a better 5-year overall survival (87.7% vs. 73.9%, p = .012) and disease-free survival (64.1% vs. 51.3%, p = .013) than those without HP infection, especially for intestinal-type GC. For EBV-negative GC, patients with HP infection had fewer PI3K/AKT pathway mutations and a better 5-year overall survival and disease-free survival than those without HP infection. Multivariate analysis demonstrated that HP infection was an independent prognostic factor regarding overall survival and disease-free survival. CONCLUSION Patients with GC with HP infection were associated with fewer PI3K/AKT pathway genetic mutations and better survival than those without HP infection, especially for EBV-negative and intestinal-type GC. IMPLICATIONS FOR PRACTICE Patients with gastric cancer with Helicobacter pylori (HP) infection had fewer PI3K/AKT pathway genetic mutations, less tumor recurrence, and better survival than those without HP infection, especially for Epstein-Barr virus (EBV)-negative and intestinal-type gastric cancer. HP infection is an independent prognostic factor regarding overall survival and disease-free survival. Future in vivo and in vitro studies of the correlation among HP infection, PI3K/AKT pathway, and EBV infection in gastric cancer are required.
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Affiliation(s)
- Wen-Liang Fang
- Division of General Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan
| | - Kuo-Hung Huang
- Division of General Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan
| | - Shih-Ching Chang
- Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan
| | - Chien-Hsing Lin
- Genome Research Center, National Yang-Ming University, Taipei City, Taiwan
| | - Ming-Huang Chen
- Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan
| | - Yee Chao
- Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan
| | - Su-Shun Lo
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan
- National Yang-Ming University Hospital, Yilan City, Taiwan
| | - Anna Fen-Yau Li
- Department of Pathology, Taipei Veterans General Hospital, Taipei City, Taiwan
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan
| | - Chew-Wun Wu
- Division of General Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan
| | - Yi-Ming Shyr
- Division of General Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan
- School of Medicine, National Yang-Ming University, Taipei City, Taiwan
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Sun X, Xiang CJ, Wu J, Dong W, Zhan Z, Wang RP, Zhang JF. Relationship between serum inflammatory cytokines and lifestyle factors in gastric cancer. Mol Clin Oncol 2019; 10:401-414. [PMID: 30847182 DOI: 10.3892/mco.2019.1804] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 01/15/2019] [Indexed: 12/15/2022] Open
Abstract
Chronic inflammation is associated with increased risk of gastric cancer (GC), and GC risk is significantly associated with lifestyle. The aim of the present study was to explore the association between serum inflammatory cytokines and lifestyle factors in GC. A total of 20 serum inflammatory cytokines were measured in a hospital-based case-control population with 142 GC patients and 98 healthy controls. Controls without the selected healthy lifestyle factors were regarded as baseline, and correlation analysis was conducted to establish the association between serum inflammatory cytokines and lifestyle factors. The results demonstrated that several lifestyle factors (including eating fried and salty foods, eating quickly, smoking and drinking) could increase the risk of GC, while only eating fresh fruits could decrease the risk of GC. Correlation analysis revealed that increased serum interleukin (IL)-12/IL-23P40 levels was associated with GC risk as significant differences were observed in all lifestyle factors. Increased serum IL-8 was closely associated with smoking in GC patients, while increased IL-17α and IL-8 levels were associated with GC patients who ate salty foods. Increased IL-10 and decreased TGF-β levels were also associated with GC patients who ate fresh fruits. In conclusion, GC risk was strongly affected by lifestyle factors, which may regulate the expression of inflammatory cytokines and promote gastric carcinogenesis.
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Affiliation(s)
- Xian Sun
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Chun-Jie Xiang
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Juan Wu
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Wei Dong
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Zhen Zhan
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
| | - Rui-Ping Wang
- Department of Oncology, First Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China.,Department of Oncology, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, P.R. China
| | - Jun-Feng Zhang
- Department of Pathogen and Immunology, School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
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29
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Yamada A, Kaise M, Inoshita N, Toba T, Nomura K, Kuribayashi Y, Yamashita S, Furuhata T, Kikuchi D, Matsui A, Mitani T, Ogawa O, Iizuka T, Hoteya S. Characterization of Helicobacter pylori-Naïve Early Gastric Cancers. Digestion 2018; 98:127-134. [PMID: 29719284 DOI: 10.1159/000487795] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 02/16/2018] [Indexed: 02/04/2023]
Abstract
AIM Helicobacter pylori-naïve gastric cancers(GCs) have not been well documented. We aimed to characterize early H. pylori-naïve GCs. SUBJECTS AND METHODS Of 666 patients with GC resected by endoscopic submucosal dissection, H. pylori-naïve patients were extracted according to the definition: no H. pylori eradication history, negative for serum H. pylori-antibody and current H. pylori-infection tests, and no gastric atrophy by pepsinogen (PG) test, endoscopy, and histology. RESULTS It was found that 16 GCs were H. pylori-naïve, and classified into undifferentiated and differentiated type adenocarcinoma. All 9 undifferentiated type GCs were pale, depressed, mucosal pure signet ring cell adenocarcinoma except one of them and 7 differentiated type GCs were classified into 3 fundic gland type GCs and 4 foveolar type GCs. All fundic gland type GCs positive for PG-1 were cardia small submucosal tumor (SMT)-like protrusions with dilated vessels on the surface. All 4 foveolar type GCs were composed of dysplastic clear cells resembling foveolar epithelium, negative for PG-1 but positive for mucin 6 (MUC6) and MUC5AC. Endoscopically, all were laterally spreading elevations with papillary or villous surface. CONCLUSIONS H. pylori-naïve GCs were infrequent at 2.5%, and classified into 3 types: a small pale depression of signet ring cell adenocarcinoma, a small SMT-like protrusion of fundic gland type GC, and a large laterally spreading elevation of foveolar type GC.
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Affiliation(s)
- Akihiro Yamada
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Mitsuru Kaise
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Naoko Inoshita
- Department of Pathology, Toranomon Hospital, Tokyo, Japan
| | - Takahito Toba
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Kosuke Nomura
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | | | | | - Tsukasa Furuhata
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Daisuke Kikuchi
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Akira Matsui
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Toshifumi Mitani
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Osamu Ogawa
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Toshiro Iizuka
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
| | - Shu Hoteya
- Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
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30
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Jung DH, Lee YC, Kim JH, Chung H, Park JC, Shin SK, Lee SK, Kim HI, Hyung WJ, Noh SH. Postoperative Helicobacter pylori Infection as a Prognostic Factor for Gastric Cancer Patients after Curative Resection. Gut Liver 2018; 11:635-641. [PMID: 28395509 PMCID: PMC5593325 DOI: 10.5009/gnl16397] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 09/27/2016] [Accepted: 11/12/2016] [Indexed: 02/01/2023] Open
Abstract
Background/Aims Few studies have evaluated the effect of Helicobacter pylori infection on the prognosis of patients diagnosed with gastric cancer (GC) after curative surgery. We investigated the association between the H. pylori infection status and clinical outcome after surgery. Methods We assessed the H. pylori status of 314 patients who underwent curative resection for GC. The H. pylori status was examined using a rapid urease test 2 months after resection. Patients were followed for 10 years after surgery. Results An H. pylori infection was observed in 128 of 314 patients. The median follow-up period was 93.5 months. A Kaplan-Meier analysis indicated that patients with H. pylori had a higher cumulative survival rate than those who were negative for H. pylori. Patients with stage II cancer who tested negative for H. pylori were associated with a poor outcome. In a multivariate analysis, H. pylori-negative status was a significant independent prognostic factor for poor overall survival. Conclusions Having a negative H. pylori infection status seems to indicate poor prognosis for patients with GC who have undergone curative resection. Further prospective controlled studies are needed to evaluate the mechanism by which H. pylori affects GC patients after curative surgery in Korea.
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Affiliation(s)
- Da Hyun Jung
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jie-Hyun Kim
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyunsoo Chung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Chul Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Kwan Shin
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Kil Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyoung-Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Woo Jin Hyung
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hoon Noh
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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31
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Nishizuka SS, Tamura G, Nakatochi M, Fukushima N, Ohmori Y, Sumida C, Iwaya T, Takahashi T, Koeda K. Helicobacter pylori infection is associated with favorable outcome in advanced gastric cancer patients treated with S-1 adjuvant chemotherapy. J Surg Oncol 2018; 117:947-956. [PMID: 29355977 DOI: 10.1002/jso.24977] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 12/11/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Limited information exists regarding beneficial effects of Helicobacter pylori. To examine the effect in advanced gastric cancer, we compared survival for patients treated with surgery-only or adjuvant chemotherapy on the basis of H. pylori infection status. METHODS A cohort of 491 patients who underwent R0 resection for locally advanced gastric cancer between 2000 and 2009 at 12 institutions in northern Japan was included. H. pylori infection status, was assessed from paraffin-embedded formalin-fixed samples. Overall survival (OS) and disease-free survival (DFS) in surgery-only (Surgery) and adjuvant chemotherapy (S-1) groups were analyzed. A propensity score matching was employed to correct for confounding factors by indication. RESULTS H. pylori infection was positive in 175 patients and negative in 316 patients. H. pylori-positive patients showed significantly better survival than H. pylori-negative patients in both OS (hazard ratio [HR] 0.593, 95% confidence interval [CI] 0.417-0.843; P = 0.003]) and DFS (HR 0.679, 95%CI 0.492-0.937; P = 0.018). Propensity score matching further confirmed that S-1 was virtually only effective when tumors were H. pylori-positive. CONCLUSIONS The favorable outcome of H. pylori-positive patients implies that the host immune system is modulated by H. pylori enhancing the chemotherapeutic efficacy.
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Affiliation(s)
- Satoshi S Nishizuka
- Molecular Therapeutics Laboratory, Iwate Medical University School of Medicine, Morioka, Japan.,Department of Surgery, Iwate Medical University School of Medicine, Morioka, Japan.,Division of Biomedical Research & Development, Institute of Biomedical Sciences, Iwate Medical University, Morioka, Japan.,Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia
| | - Gen Tamura
- Department of Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan
| | - Masahiro Nakatochi
- Statistical Analysis Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan
| | - Norimasa Fukushima
- Department of Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan
| | - Yukimi Ohmori
- Molecular Therapeutics Laboratory, Iwate Medical University School of Medicine, Morioka, Japan
| | - Chihiro Sumida
- Molecular Therapeutics Laboratory, Iwate Medical University School of Medicine, Morioka, Japan
| | - Takeshi Iwaya
- Molecular Therapeutics Laboratory, Iwate Medical University School of Medicine, Morioka, Japan.,Department of Surgery, Iwate Medical University School of Medicine, Morioka, Japan
| | - Takashi Takahashi
- Division of Molecular Carcinogenesis, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Keisuke Koeda
- Department of Surgery, Iwate Medical University School of Medicine, Morioka, Japan
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32
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Leung WK, Ho HJ, Lin JT, Wu MS, Wu CY. Prior gastroscopy and mortality in patients with gastric cancer: a matched retrospective cohort study. Gastrointest Endosc 2018. [PMID: 28648576 DOI: 10.1016/j.gie.2017.06.013] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The role of prior gastroscopy on the outcome of patients with gastric cancer remains unknown. This study determines the association between intervals of prior gastroscopy and mortality in patients with gastric cancer. METHODS We identified 20,066 newly diagnosed patients with gastric cancer in the National Health Insurance Database of Taiwan between 2002 and 2007. After we excluded patients who had gastroscopies performed ≤6 months before the diagnosis of cancer, patients were matched into 3 cohorts according to the intervals of prior gastroscopy: 6 months to 2 years (<2 Y cohort), 2 to 5 years (2-5 Y cohort), and none within the previous 5 years (>5 Y cohort). The 3 cohorts were matched for age, curative treatment for gastric cancer, Helicobacter pylori therapy, and propensity scores comprised of sex, comorbidities, and concomitant medication usage. The primary outcome is the hazard ratio (HR) of all-cause mortality. RESULTS After matching, we identified 1286, 1286, and 5144 patients for the <2 Y, 2 to 5 Y, and >5 Y cohorts. Compared with the >5 Y cohort, the HR of all-cause mortality for the <2 Y and 2 to 5 Y cohorts was 0.80 (95% confidence interval [CI], 0.72-0.89; P < .001) and 0.83 (95% CI, 0.76-0.91; P < .001), respectively. The HRs of gastric cancer-specific mortality were significantly lower in the <2 Y (0.80; 95% CI, 0.71-0.91; P < .001) and 2 to 5 Y cohorts (0.83; 95% CI, 0.75-0.93; P < .001). CONCLUSIONS Patients with gastric cancer who had a gastroscopy performed within 5 years before the cancer diagnosis had significantly lower mortality. Our results may support the role of repeat endoscopic examination or surveillance endoscopy in selected patients.
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Affiliation(s)
- Wai K Leung
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - Hsiu J Ho
- Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, Taipei, Taiwan; Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan
| | - Ming-Shiang Wu
- Division of Gastroenterology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Ying Wu
- Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Public Health and Graduate Institute of Clinical Medical Sciences, China Medical University, Taichung, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan; Department of Life Sciences and Rong Hsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan
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33
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Petrelli F, Ghidini M, Barni S, Steccanella F, Sgroi G, Passalacqua R, Tomasello G. Prognostic Role of Primary Tumor Location in Non-Metastatic Gastric Cancer: A Systematic Review and Meta-Analysis of 50 Studies. Ann Surg Oncol 2017; 24:2655-2668. [DOI: 10.1245/s10434-017-5832-4] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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34
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Prevalence and characteristics of Epstein-Barr virus-associated gastric carcinomas in Portugal. Infect Agent Cancer 2017; 12:41. [PMID: 28814970 PMCID: PMC5518146 DOI: 10.1186/s13027-017-0151-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 07/10/2017] [Indexed: 12/17/2022] Open
Abstract
Background Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract and is the third leading cause of cancer death worldwide. Epstein–Barr virus (EBV) has been associated with approximately 10% of the total cases of gastric carcinomas. No previous study has analyzed the prevalence of EBV infection in gastric cancer of the Portuguese population. Methods In the present study, we have analyzed 82 gastric carcinoma cases and 33 healthy individuals (control group) from Coimbra region for the presence of EBV by polymerase chain reaction (PCR) and by in situ hybridization (ISH) for EBV-encoded small RNAs (EBERs). The status of H. pylori infection was assessed by serology and by PCR. Results EBV was detected by PCR in 90.2% of stomach cancer cases, whereas EBERs were detected in 11%. In our series, EBV-associated gastric carcinoma (EBVaGC) were significantly associated with gender and the majority of them presented lymph node metastasis. These cases were generally graded in more advanced pTNM stages and, non-surprisingly, showed worse survival. H. pylori infection was detected in 62.2% of the gastric cancers and 64.7% of these patients were CagA+. On the other hand, the H. pylori prevalence was higher in the EBV-negative gastric carcinomas (64.4%) than in those carcinoma cases with EBV+ (44.4%). Conclusions The present study shows that prevalence of EBVaGC among Portuguese population is in accordance with the worldwide prevalence. EBV infection seems to be associated to poorer prognostic and no relation to H. pylori infection has been found. Conversely, the presence of H. pylori seems to have a favourable impact on patient’s survival. Our results emphasize that geographic variation can contribute with new epidemiological data on the association of EBV with gastric cancer.
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35
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Fang X, Liu K, Cai J, Luo F, Yuan F, Chen P. Positive Helicobacter pylori status is associated with better overall survival for gastric cancer patients: evidence from case-cohort studies. Oncotarget 2017; 8:79604-79617. [PMID: 29108340 PMCID: PMC5668073 DOI: 10.18632/oncotarget.18758] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 05/15/2017] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori (H. pylori) infection increases the gastric cancer risk; however, the influences of H. pylori infection status on the outcomes for gastric cancer patients have not yet clearly defined. Herein, we systematically assessed the epidemiological studies regarding the associations between the H.pylori infection status at diagnosis and the prognosis for gastric cancer patients with the meta-analysis methods. Thirty-three eligibility studies with 8,199 participants that had determined the H.pylori infection status and the outcomes for gastric cancer patients were identified through searching the PubMed and MEDLINE databases updated to March 1st, 2017. The random-effects model suggested that positive H. pylori infection was associated with better overall survival with the pooled hazard ratio (HR) was 0.79 [95% confidence interval (CI) = 0.66-0.93; Q = 134.86, df = 32, P-heterogeneity < 0.001; I2 = 76.3%] compared to negative patients. The association was found to be more prominent in studies with higher quality, longer following-up time and more sensitive detection methods. An inverse but not statistically significant association between the H.pylori status and the disease-free survival of the patients (pooled HR = 0.84, 95% CI = 0.61-1.05;Q = 30.48, df = 11, P-heterogeneity = 0.001; I2 = 63.9%) was found, while no significant association was noticed in any subgroup analyses. These results suggested that gastric cancer patients with positive H.pylori infection status at diagnosis have better overall survival compared to negative; however, more studies are warranted to confirm the results and elucidate the underlying mechanisms.
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Affiliation(s)
- Xuqian Fang
- Translational Medicine Research Center, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.,Department of Pathology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Kun Liu
- Department of Surgery, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Jialin Cai
- Translational Medicine Research Center, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Fangxiu Luo
- Department of Pathology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Fei Yuan
- Department of Pathology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
| | - Peizhan Chen
- Translational Medicine Research Center, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China
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Kolb JM, Ozbek U, Harpaz N, Holcombe RF, Ang C. Effect of Helicobacter pylori infection on outcomes in resected gastric and gastroesophageal junction cancer. J Gastrointest Oncol 2017; 8:583-588. [PMID: 28736645 DOI: 10.21037/jgo.2017.01.22] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Helicobacter pylori (H pylori) infection is a known risk factor for gastric cancer (GC) and has been linked with gastroesophageal junction (GEJ) cancer. Studies examining the relationship between H. pylori infection, GC characteristics and prognosis are limited and have yielded conflicting results. We report on the clinicopathologic characteristics and oncologic outcomes of gastric and GEJ cancer patients with and without a history of H. pylori treated at our institution. METHODS We retrospectively reviewed the medical records of patients over the age of 18 years who underwent curative resection for GEJ and GC at Mount Sinai Hospital between 2007 and 2012 who had histopathologic documentation of the presence or absence of H pylori infection. Demographic, clinical, pathologic, treatment characteristics and outcomes including recurrence-free survival (RFS) and overall survival (OS) were compared. RESULTS Ninety-five patients were identified. The majority of patients were male (61%), white (36%) or Asian (34%), with median age at diagnosis 64. Tumors were stage I (51%), stage II (23%), stage III (25%), and stage IV (1%). H pylori infection status was documented at the time of cancer diagnosis in 89 (94%) patients, and following cancer diagnosis and treatment in 6 (6%) patients. Younger age at diagnosis, Asian race and Lauren histologic classification were associated with H Pylori infection. H pylori positive patients exhibited higher 5-year OS and 5-year RFS compared to H pylori negative patients, though the difference was not statistically significant in either univariate or multivariate analyses. CONCLUSIONS In this retrospective series of predominantly early stage GC and GEJ cancers, H. pylori positive patients were significantly younger at cancer diagnosis and were more frequently Asian compared to H. pylori negative patients. Other demographic and histologic classifications except for Lauren histologic classification were similar between the two groups. H pylori positive patients appeared to have improved outcomes compared to H. pylori negative patients.
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Affiliation(s)
- Jennifer M Kolb
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Umut Ozbek
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Noam Harpaz
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Celina Ang
- Department of Internal Medicine, Division of Hematology/Oncology School of Medicine at Mount Sinai, New York, NY, USA
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Bernardini G, Figura N, Ponzetto A, Marzocchi B, Santucci A. Application of proteomics to the study of Helicobacter pylori and implications for the clinic. Expert Rev Proteomics 2017; 14:477-490. [PMID: 28513226 DOI: 10.1080/14789450.2017.1331739] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric epithelium and mucous layer of more than half the world's population. H. pylori is a primary human pathogen, responsible for the development of chronic gastritis, peptic ulceration and gastric cancer. Proteomics is impacting several aspects of medical research: understanding the molecular basis of infection and disease manifestation, identification of therapeutic targets and discovery of clinically relevant biomarkers. Areas covered: The main aim of the present review is to provide a comprehensive overview of the contribution of proteomics to the study of H. pylori infection pathophysiology. In particular, we focused on the role of the bacterium and its most important virulence factor, CagA, in the progression of gastric cells transformation and cancer progression. We also discussed the proteomic approaches aimed at the investigation of the host response to bacterial infection. Expert commentary: In the field of proteomics of H. pylori, comprehensive analysis of clinically relevant proteins (functional proteomics) rather than entire proteomes will result in important medical outcomes. Finally, we provided an outlook on the potential development of proteomics in H. pylori research.
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Affiliation(s)
- Giulia Bernardini
- a Dipartimento di Biotecnologie , Chimica e Farmacia, Università degli Studi di Siena , Siena , Italy
| | - Natale Figura
- a Dipartimento di Biotecnologie , Chimica e Farmacia, Università degli Studi di Siena , Siena , Italy
| | - Antonio Ponzetto
- b Dipartimento di Scienze Mediche , Università degli Studi di Torino , Torino , Italy
| | - Barbara Marzocchi
- a Dipartimento di Biotecnologie , Chimica e Farmacia, Università degli Studi di Siena , Siena , Italy
| | - Annalisa Santucci
- a Dipartimento di Biotecnologie , Chimica e Farmacia, Università degli Studi di Siena , Siena , Italy
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Jia ZF, Wu YH, Cao DH, Cao XY, Jiang J, Zhou BS. Polymorphisms of cancer stem cell marker gene CD133 are associated with susceptibility and prognosis of gastric cancer. Future Oncol 2017; 13:979-989. [PMID: 28326835 DOI: 10.2217/fon-2017-0019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM This study was aimed to investigate the associations between single nucleotide polymorphisms of cancer stem cell marker genes, CD44 and CD133, and susceptibility and prognosis of gastric cancer. PATIENTS & METHODS Five single nucleotide polymorphisms in CD44 and CD133 genes were genotyped in 898 gastric cancer cases and 992 controls. RESULTS The A/C or C/C genotypes of CD133 rs2240688 were associated with decreased risk of gastric cancer comparing with the A/A genotype (odds ratio: 0.81; 95% CI: 0.67-0.97; p = 0.023). The T allele of CD133 rs3130 predicted a worse survival for gastric cancer patients receiving tumorectomy (hazard ratio: 1.28; 95% CI: 1.04-1.58; p = 0.020), independent from tumor node metastasis stage, vessel invasion and postoperational chemotherapy. CONCLUSION CD133 polymorphisms are promising biomarkers for genetic susceptibility and prognosis prediction of gastric cancer.
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Affiliation(s)
- Zhi-Fang Jia
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110112, PR China.,Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, PR China
| | - Yan-Hua Wu
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, PR China
| | - Dong-Hui Cao
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, PR China
| | - Xue-Yuan Cao
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun 130021, PR China
| | - Jing Jiang
- Division of Clinical Research, First Hospital of Jilin University, Changchun 130021, PR China
| | - Bao-Sen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110112, PR China
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Tsai KF, Liou JM, Chen MJ, Chen CC, Kuo SH, Lai IR, Yeh KH, Lin MT, Wang HP, Cheng AL, Lin JT, Shun CT, Wu MS. Distinct Clinicopathological Features and Prognosis of Helicobacter pylori Negative Gastric Cancer. PLoS One 2017; 12:e0170942. [PMID: 28152027 PMCID: PMC5289528 DOI: 10.1371/journal.pone.0170942] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 01/12/2017] [Indexed: 12/17/2022] Open
Abstract
Background Whether the characteristics and prognosis of gastric cancer (GC) are different in patients with and without Helicobacter pylori (HP) remains controversial. The definitions of HP status in patients with atrophic gastritis but negative tests for HP are heterogeneous. We aimed to assess the impact of HP on the prognosis of GC using different definitions. Methods From 1998 Nov to 2011 Jul, five hundred and sixty-seven consecutive patients with GC were included. HP status was determined by serology and histology. Patients with any positive test were defined as HP infection. Patients without HP infection whose serum pepsinogen (PG) I <70 ng/dl and PG I/II ratio < 3.0 were defined as atrophic gastritis and they were categorized into model 1: HP positive; model 2: HP negative; and model 3: exclusion of these patients. Results We found four characteristics of HP negative GC in comparison to HP positive GC: (1) higher proportion of the proximal tumor location (24.0%, P = 0.004), (2) more diffuse histologic type (56.1%, p = 0.008), (3) younger disease onset (58.02 years, p = 0.008) and (4) more stage IV disease (40.6%, p = 0.03). Patients with negative HP had worse overall survival (24.0% vs. 35.8%, p = 0.035). In Cox regression models, the negative HP status is an independent poor prognostic factor (HR: 1.34, CI:1.04–1.71, p = 0.019) in model 1, especially in stage I, II and III patients (HR: 1.62; CI:1.05–2.51,p = 0.026). Conclusion We found the distinct characteristics of HP negative GC. The prognosis of HP negative GC was poor.
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Affiliation(s)
- Kun-Feng Tsai
- Department of Internal Medicine, Gastroenterology and Hepatology Section, An Nan Hospital, China Medical University, Tainan, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Jyh-Ming Liou
- Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Jyh Chen
- Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Chuan Chen
- Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Sung-Hsin Kuo
- Department of Oncology, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - I-Rue Lai
- Department of Surgery, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Kun-Huei Yeh
- Department of Oncology, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Tsan Lin
- Department of Surgery, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Ann-Lii Cheng
- Department of Oncology, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Jaw-Town Lin
- Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Chia-Tung Shun
- Department of Pathology and Forensic Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
- * E-mail: (MSW); (CTS)
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
- * E-mail: (MSW); (CTS)
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Kim HJ, Kim N, Yoon H, Choi YJ, Lee JY, Kwon YH, Yoon K, Jo HJ, Shin CM, Park YS, Park DJ, Kim HH, Lee HS, Lee DH. Comparison between Resectable Helicobacter pylori-Negative and -Positive Gastric Cancers. Gut Liver 2016; 10:212-9. [PMID: 26087794 PMCID: PMC4780450 DOI: 10.5009/gnl14416] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS Controversy exists regarding the characteristics of Helicobacter pylori infection-negative gastric cancer (HPIN-GC). The aim of this study was to evaluate clinicopathologic features of HPIN-GC compared to H. pylori infection-positive gastric cancer (HPIP-GC) using a comprehensive analysis that included genetic and environmental factors. METHODS H. pylori infection status of 705 resectable gastric cancer patients was determined by the rapid urease test, testing for anti-H. pylori antibodies, histologic analysis and culture of gastric cancer tissue samples, and history of H. pylori eradication. HPIN-GC was defined as gastric cancer that was negative for H. pylori infection based on all five methods and that had no evidence of atrophy in histology or serology. RESULTS The prevalence of HPIN-GC was 4% (28/705). No significant differences with respect to age, sex, smoking, drinking, family history of gastric cancer or obesity were observed between the two groups. HPIN-GC tumors were marginally more likely to involve the cardia (14.3% for HPIN-GC vs 5.3% for HPIP-GC, p=0.068). The Lauren classification, histology, and TNM stage did not differ according to H. pylori infection status. Microsatellite instability was not different between the two groups, but p53 overexpression in HPIN-GC was marginally higher than in HPIP-GC (56.0% for HPIN-GC vs 37.0% for HPIP-GC, p=0.055). CONCLUSIONS The prevalence of HPIN-GC was extremely low, and its clinicopathologic characteristics were similar to HPIP-GC.
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Affiliation(s)
- Hee Jin Kim
- Department of Internal Medicine, Myongji Hospital, Goyang, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jin Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ju Yup Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yong Hwan Kwon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kichul Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyun Jin Jo
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyung Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
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Okano A, Kato S, Ohana M. Helicobacter pylori-negative gastric cancer: advanced-stage undifferentiated adenocarcinoma located in the pyloric gland area. Clin J Gastroenterol 2016; 10:13-17. [PMID: 27783218 DOI: 10.1007/s12328-016-0696-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Accepted: 10/13/2016] [Indexed: 12/13/2022]
Abstract
The incidence of Helicobacter pylori-negative gastric cancer (HpNGC) is extremely low. A 78-year old female without H. pylori infection was diagnosed with type 4 advanced-stage gastric prepylorus cancer. Distal gastrectomy was performed as for HpNGC (cT3N0M0). Histological findings of the resected specimen showed poorly differentiated adenocarcinoma and signet ring cell carcinoma, which were located in the pyloric gland area, diffusely invaded beyond the serosa without lymph node metastasis (pT4aN0M0). Most cases of undifferentiated-type HpNGC are diagnosed in the early stage and are located in the fundic gland area. We report the first case of advanced-stage undifferentiated HpNGC located in the pyloric gland area.
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Affiliation(s)
- Akihiro Okano
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara, 632-8552, Japan.
| | - Shigeru Kato
- Department of Gastroenterological Surgery, Tenri Hospital, Tenri, Japan
| | - Masaya Ohana
- Department of Gastroenterology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara, 632-8552, Japan
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Ma HY, Liu XZ, Liang CM. Inflammatory microenvironment contributes to epithelial-mesenchymal transition in gastric cancer. World J Gastroenterol 2016; 22:6619-6628. [PMID: 27547005 PMCID: PMC4970470 DOI: 10.3748/wjg.v22.i29.6619] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/12/2016] [Accepted: 07/06/2016] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer (GC) is the fifth most common malignancy in the world. The major cause of GC is chronic infection with Helicobacter pylori (H. pylori). Infection with H. pylori leads to an active inflammatory microenvironment that is maintained by immune cells such as T cells, macrophages, natural killer cells, among other cells. Immune cell dysfunction allows the initiation and accumulation of mutations in GC cells, inducing aberrant proliferation and protection from apoptosis. Meanwhile, immune cells can secrete certain signals, including cytokines, and chemokines, to alter intracellular signaling pathways in GC cells. Thus, GC cells obtain the ability to metastasize to lymph nodes by undergoing the epithelial-mesenchymal transition (EMT), whereby epithelial cells lose their epithelial attributes and acquire a mesenchymal cell phenotype. Metastasis is a leading cause of death for GC patients, and the involved mechanisms are still under investigation. In this review, we summarize the current research on how the inflammatory environment affects GC initiation and metastasis via EMT.
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Intestinal-type gastric adenocarcinoma without Helicobacter pylori infection successfully treated with endoscopic submucosal dissection. Clin J Gastroenterol 2016; 9:228-32. [PMID: 27259702 DOI: 10.1007/s12328-016-0654-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 05/14/2016] [Indexed: 12/13/2022]
Abstract
A 67-year-old woman was admitted to our hospital for further examination and for treatment of gastric neoplasia located on the posterior wall of the antrum of the stomach, as revealed by screening esophagogastroduodenoscopy. The patient had no history of Helicobacter pylori (H. pylori) eradication. Her serum H. pylori antibody and urea breath test results were negative, histopathological findings revealed no H. pylori bacteria, and endoscopic findings revealed no chronic gastritis. We performed endoscopic submucosal dissection (ESD). Histological examination of the resected tissues revealed the tumor to be composed of a well-differentiated tubular adenocarcinoma with a tubular-type adenoma confined to the mucosa. This adenocarcinoma exhibited immunohistochemical expression of CD10, MUC2, and Cdx2, but not MUC5AC or MUC6. This is an extremely rare case of H. pylori infection-negative, intestinal-type, differentiated gastric adenocarcinoma revealed by detailed immunohistochemical examination that was treated with ESD. The patient has had no recurrence of adenocarcinoma after ESD.
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Chang H, Kim N, Park JH, Nam RH, Choi YJ, Lee HS, Yoon H, Shin CM, Park YS, Kim JM, Lee DH. Different microRNA expression levels in gastric cancer depending on Helicobacter pylori infection. Gut Liver 2015; 9:188-96. [PMID: 25167801 PMCID: PMC4351025 DOI: 10.5009/gnl13371] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND/AIMS This study was conducted to identify microRNAs (miRNAs) that are differentially expressed in Helicobacter pylori-infected patients with an intestinal type of gastric cancer using miRNA microarray and to confirm the candidate miRNA expression levels. METHODS Total RNA was extracted from the cancerous and noncancerous regions of formalin-fixed, paraffin-embedded tissues of H. pylori-positive (n=8) or H. pylori-negative (n=8) patients with an intestinal type of gastric cancer. RNA expression was analyzed using a 3,523 miRNA profiling microarray based on the Sanger miRBase. Validation analysis was performed using TaqMan miRNA assays. RESULTS A total of 219 miRNAs in the aber-rant miRNA profiles across the miRNA microarray showed at least a 2-fold change differential expression in H. pylori-positive and H. pylori-negative cancer tissues. After candi-date miRNAs were selected using online miRNA databases, TaqMan miRNA assays confirmed that three miRNAs (miR-99b-3p, miR-564, and miR-638) were significantly increased in three H. pylori-positive cancer tissues compared to the H. pylori-negative cancer tissues. Additionally, four miRNAs (miR-204-5p, miR-338-5p, miR-375, and miR-548c-3p) were significantly increased in H. pylori-negative cancer tissues compared to H. pylori-positive cancer tissues. CONCLUSIONS miRNA expression in the intestinal type of H. pylori infection-dependent gastric cancer suggests that different gastric can-cer pathogenesis mechanisms could exist between H. pylori-positive and H. pylori-negative gastric cancer. Additional functional studies are required. (Gut Liver, 2015;9188-196).
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Affiliation(s)
- Hyun Chang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam and Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yoon Jeong Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam and Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jung Min Kim
- NAR Center, Inc., Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam and Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Kim YI, Cho SJ, Lee JY, Kim CG, Kook MC, Ryu KW, Kim YW, Choi IJ. Effect of Helicobacter pylori Eradication on Long-Term Survival after Distal Gastrectomy for Gastric Cancer. Cancer Res Treat 2015; 48:1020-9. [PMID: 26582396 PMCID: PMC4946357 DOI: 10.4143/crt.2015.264] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2015] [Accepted: 10/27/2015] [Indexed: 12/18/2022] Open
Abstract
Purpose Negative Helicobacter pylori status has been identified as a poor prognostic factor for survival in gastric cancer (GC) patients who underwent surgery. The aim of this study was to examine the effect of H. pylori eradication on long-term outcomes after distal gastrectomy for GC. Materials and Methods We analyzed the survival of 169 distal GC patients enrolled in a prospective randomized trial evaluating histologic changes of gastric mucosa after H. pylori eradication in the remnant stomach. The outcomes measured were overall survival (OS) and GC recurrence rates. Results The median follow-up duration was 9.4 years. In the modified intention-to-treat analysis including patients who underwent H. pylori treatment (n=87) or placebo (n=82), 5-year OS rates were 98.9% in the treatment group and 91.5% in the placebo group, and Kaplan-Meier analysis showed no significant difference in OS (p=0.957) between groups. In multivariate analysis, no difference in overall mortality was observed between groups (adjusted hazard ratio [aHR] for H. pylori treatment, 0.75; p=0.495) or H. pylori-eradicated status (aHR for positive H. pylori status, 1.16; p=0.715), while old age, male sex, and advanced stage ≥ IIIa were independent risk factors. Six patients in the treatment group (6.9%) and seven patients in the placebo group (8.5%) had GC recurrences, and GC recurrence rates were not different according to H. pylori treatment (5-year GC recurrence rates, 4.6% in the treatment group vs. 8.5% in the placebo group; p=0.652). Conclusion H. pylori eradication for GC patients who underwent distal gastrectomy did not compromise long-term survival after surgery.
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Affiliation(s)
- Young-Il Kim
- Center for Gastric Cancer, National Cancer Center, Korea
| | - Soo-Jeong Cho
- Center for Gastric Cancer, National Cancer Center, Korea
| | - Jong Yeul Lee
- Center for Gastric Cancer, National Cancer Center, Korea
| | - Chan Gyoo Kim
- Center for Gastric Cancer, National Cancer Center, Korea
| | | | - Keun Won Ryu
- Center for Gastric Cancer, National Cancer Center, Korea
| | - Young-Woo Kim
- Center for Gastric Cancer, National Cancer Center, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center, Korea
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Postlewait LM, Squires MH, Kooby DA, Poultsides GA, Weber SM, Bloomston M, Fields RC, Pawlik TM, Votanopoulos KI, Schmidt CR, Ejaz A, Acher AW, Worhunsky DJ, Saunders N, Swords D, Jin LX, Cho CS, Winslow ER, Cardona K, Staley CA, Maithel SK. Preoperative Helicobacter pylori Infection is Associated with Increased Survival After Resection of Gastric Adenocarcinoma. Ann Surg Oncol 2015; 23:1225-33. [PMID: 26553442 DOI: 10.1245/s10434-015-4953-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND Limited data exist on the prognosis of preoperative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC). METHODS Patients who underwent curative-intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the United States Gastric Cancer Collaborative were included in the study. The primary end points of the study were overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS). RESULTS Of 559 patients, 104 (18.6 %) who tested positive for H. pylori were younger (62.1 vs 65.1 years; p = 0.041), had a higher frequency of distal tumors (82.7 vs 71.9 %; p = 0.033), and had higher rates of adjuvant radiation therapy (47.0 vs 34.9 %; p = 0.032). There were no differences in American Society of Anesthesiology (ASA) class, margin status, grade, perineural invasion, lymphovascular invasion, nodal metastases, or tumor-node-metastasis (TNM) stage. H. pylori positivity was associated with longer OS (84.3 vs 44.2 months; p = 0.008) for all patients. This relationship with OS persisted in the multivariable analysis (HR 0.54; 95 % CI 0.30-0.99; p = 0.046). H. pylori was not associated with RFS or DSS in all patients. In the stage 3 patients, H. pylori was associated with longer OS (44.5 vs 24.7 months; p = 0.018), a trend of longer RFS (31.4 vs 21.6 months; p = 0.232), and longer DSS (44.8 vs 27.2 months; p = 0.034). CONCLUSIONS Patients with and without preoperative H. pylori infection had few differences in adverse pathologic features at the time of gastric adenocarcinoma resection. Despite similar disease presentations, preoperative H. pylori infection was independently associated with improved OS. Further studies examining the interaction between H. pylori and tumor immunology and genetics are merited.
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Affiliation(s)
- Lauren M Postlewait
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Malcolm H Squires
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - George A Poultsides
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - Sharon M Weber
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Mark Bloomston
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Ryan C Fields
- Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Timothy M Pawlik
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | | | - Carl R Schmidt
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Aslam Ejaz
- Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA
| | - Alexandra W Acher
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - David J Worhunsky
- Department of Surgery, Stanford University Medical Center, Stanford, CA, USA
| | - Neil Saunders
- Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Douglas Swords
- Department of Surgery, Wake Forest University, Winston-Salem, NC, USA
| | - Linda X Jin
- Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA
| | - Clifford S Cho
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Emily R Winslow
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Kenneth Cardona
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Charles A Staley
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
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Turanli S, Bozdogan N, Mersin H, Berberoglu U. The Effect of Helicobacter pylori on Gastric Cancer Treated with Adjuvant Chemotherapy After Curative Resection. Indian J Surg 2015; 77:489-94. [PMID: 26884656 DOI: 10.1007/s12262-015-1305-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 06/09/2015] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori has been associated with diverse pathologies of varying severity. We investigated the H. pylori infection status and its association with the pathologic features and clinical outcomes in stage III gastric cancer patients treated with adjuvant therapy after curative resection. Between 2004 and 2009, the records of 76 consecutive patients were retrospectively reviewed. H. pylori infection was confirmed by examination of pathological specimen. The relationship between H. pylori and the clinicopathological features was analyzed by Fisher exact test, Student's t test, and Kaplan-Meier method. Of the 76 patients, 16 patients (21.1 %) were confirmed for H. pylori infection. The median age was 59 years. Twenty-three patients received chemotherapy and remainder received chemoradiotherapy. H. pylori status did not correlate with the clinicopathologic features. It was greater in non-neoplastic tissue than the tumor tissue (21.1 vs 7.9 %). Median follow-up was 21 months. During this period, 88.2 % patients had experienced tumor recurrence, and 85.5 % patients had died. Recurrence was observed in 87.5 % patients and in 88.3 % patients in H. pylori-positive and H. pylori-negative patients, respectively (P = 0.92). Disease-free survival was 28.4 ± 7.9 months and overall survival was 31.5 ± 7.4 months in H. pylori-positive patients compared with 28.3 ± 3.7 and 33.2 ± 3.4 months, respectively, in H. pylori-negative patients. H. pylori infection status did not have effect on the overall or disease-free survival (p = 0.85 and P = 0.86), respectively. H. pylori status might not be useful as a prognostic and predictive factor for clinical outcomes.
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Affiliation(s)
- Sevim Turanli
- Department of General Surgery, Ankara Oncology Education and Research Hospital, 06200 Demetevler, Ankara, Turkey
| | - Nazan Bozdogan
- Department of Pathology, Ankara Oncology Education and Research Hospital, 06200 Demetevler, Ankara, Turkey
| | - Hakan Mersin
- Department of General Surgery, Ankara Oncology Education and Research Hospital, 06200 Demetevler, Ankara, Turkey
| | - Ugur Berberoglu
- Department of General Surgery, Ankara Oncology Education and Research Hospital, 06200 Demetevler, Ankara, Turkey
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Should adenocarcinoma of the esophagogastric junction be classified as gastric or esophageal cancer, or else as a distinct clinical entity? Ann Surg 2015; 261:e107-8. [PMID: 24441809 DOI: 10.1097/sla.0000000000000524] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Eun CS, Kim BK, Han DS, Kim SY, Kim KM, Choi BY, Song KS, Kim YS, Kim JF. Differences in gastric mucosal microbiota profiling in patients with chronic gastritis, intestinal metaplasia, and gastric cancer using pyrosequencing methods. Helicobacter 2014; 19:407-16. [PMID: 25052961 DOI: 10.1111/hel.12145] [Citation(s) in RCA: 219] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection plays an important role in the early stage of cancer development. However, various bacteria that promote the synthesis of reactive oxygen and nitrogen species may be involved in the later stages. We aimed to determine the microbial composition of gastric mucosa from the patients with chronic gastritis, intestinal metaplasia, and gastric cancer using 454 GS FLX Titanium. METHODS Gastric mucosal biopsy samples were collected from 31 patients during endoscopy. After the extraction of genomic DNA, variable region V5 of the 16S rRNA gene was amplified. PCR products were sequenced using 454 high-throughput sequencer. The composition, diversity, and richness of microbial communities were compared between three groups. RESULTS The composition of H. pylori-containing Epsilonproteobacteria class appeared to be the most prevalent, but the relative increase in the Bacilli class in the gastric cancer group was noticed, resulting in a significant difference compared with the chronic gastritis group. By analyzing the Helicobacter-dominant group at a family level, the relative abundance of Helicobacteraceae family was significantly lower in the gastric cancer group compared with chronic gastritis and intestinal metaplasia groups, while the relative abundance of Streptococcaceae family significantly increased. In a UPGMA clustering of Helicobacter-dominant group based on UniFrac distance, the chronic gastritis group and gastric cancer group were clearly separated, while the intestinal metaplasia group was distributed in between the two groups. The evenness and diversity of gastric microbiota in the gastric cancer group was increased compared with other groups. CONCLUSIONS In Helicobacter predominant patients, the microbial compositions of gastric mucosa from gastric cancer patients are significantly different to chronic gastritis and intestinal metaplasia patients. These alterations of gastric microbial composition may play an important, as-yet-undetermined role in gastric carcinogenesis of Helicobacter predominant patients.
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Affiliation(s)
- Chang Soo Eun
- Department of Internal Medicine, Hanyang University Guri Hospital, Gyeonggi-Do, Korea
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Kim HJ, Hwang SW, Kim N, Yoon H, Shin CM, Park YS, Lee DH, Park DJ, Kim HH, Kim JS, Jung HC, Lee HS. Helicobacter pylori and Molecular Markers as Prognostic Indicators for Gastric Cancer in Korea. J Cancer Prev 2014; 19:56-67. [PMID: 25337573 PMCID: PMC4189474 DOI: 10.15430/jcp.2014.19.1.56] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Revised: 03/18/2014] [Accepted: 03/18/2014] [Indexed: 12/01/2022] Open
Abstract
Background: The prognosis of H. pylori infection-negative gastric cancer (HPIN-GC) has been rarely investigated. Applying a strict definition of H. pylori status, the prognosis and molecular prognostic markers in HPIN-GC were evaluated. Methods: A combination of multiple methods was carried out to strictly evaluate H. pylori infection in gastric cancer (GC) patients between June 2003 and October 2012 at Seoul National University Bundang Hospital. H. pylori infection was defined as negative if histology, a rapid urease test, culturing, serology and history of H. pylori eradication were all negative. Patients with severe gastric atrophy by the serum pepsinogen test or histology were assumed to have had a previous H. pylori infection. Epstein-Barr virus (EBV) in situ hybridization, PCR-based microsatellite instability (MSI) testing, and p53 immunohistochemistry were performed. Results: Compared to 509 H. pylori infection-positive gastric cancer (HPIN-PC) patients, 24 HPIN-GC patients showed a significantly higher frequency of cardia location (P=0.013), and the depth of invasion in HPIN-GC was more advanced, although there was no statistical significance (pT3-pT4, 37.5% for HPIN-GC vs. 28.5% for HPIP-GC, P=0.341). In multivariate analysis, depth of invasion and lymph node metastasis were identified as the most important prognostic factors for relapse-free survival and overall survival (P<0.001). However, the status of H. pylori infection was not an independent prognostic factor for relapse-free survival and overall survival. The positivity of EBV in both groups was low, and the survivals according to MSI and p53 status in HPIN-GC patients were not significantly different. Conclusions: The status of H. pylori infection was not a prognostic factor for survival in GC patients when applying the strict definition of H. pylori infection. The prognostic implication of MSI and p53 on survival in HPIN-GC patients was not clear.
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Affiliation(s)
- Hee Jin Kim
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Sung Wook Hwang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Nayoung Kim
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyuk Yoon
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Cheol Min Shin
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Young Soo Park
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam
| | - Dong Ho Lee
- Departments of Internal Medicine, Seoul National University Bundang Hospital, Seongnam ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Do Joong Park
- Surgery, Seoul National University Bundang Hospital, Seongnam
| | - Hyung Ho Kim
- Surgery, Seoul National University Bundang Hospital, Seongnam
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Seung Lee
- Pathology, Seoul National University Bundang Hospital, Seongnam
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