Comparison of the Clinicopathological Characteristics and Genetic Alterations Between Patients with Gastric Cancer with or Without Helicobacter pylori Infection

Author:

Fang Wen-Liang12,Huang Kuo-Hung12,Chang Shih-Ching32,Lin Chien-Hsing4,Chen Ming-Huang52,Chao Yee52,Lo Su-Shun26,Li Anna Fen-Yau72,Wu Chew-Wun12,Shyr Yi-Ming12

Affiliation:

1. Division of General Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan

2. School of Medicine, National Yang-Ming University, Taipei City, Taiwan

3. Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei City, Taiwan

4. Genome Research Center, National Yang-Ming University, Taipei City, Taiwan

5. Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan

6. National Yang-Ming University Hospital, Yilan City, Taiwan

7. Department of Pathology, Taipei Veterans General Hospital, Taipei City, Taiwan

Abstract

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.

Funder

Division of Experimental Surgery of the Department of Surgery, Taipei Veterans General Hospital

Ministry of Science and Technology, Taiwan

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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