Molecular profile of gastric adenocarcinoma, relevant epidemiological factors - Systematic review and meta-analysis relating sex with Epstein-Barr virus and unstable microsatellites subtypes

Asia Pac J Clin Oncol. 2024 Feb;20(1):109-118. doi: 10.1111/ajco.14032. Epub 2023 Nov 6.

Abstract

Introduction: Gastric epithelial tumors exhibit morphological heterogeneity, diverse biological behaviors, and different oncopathological pathways. The Cancer Genome Atlas (TCGA) proposed a molecular classification of gastric adenocarcinomas based on genetic and molecular findings, which shows particular characteristics of diagnosis, prognosis, and indirectly, therapeutic alternatives. Within this classification, Epstein-Barr virus-positive (EBV+) and high microsatellite instability (MSI-H) subtypes stand out as subtypes that present a less aggressive biological behavior and a highly mutilated phenotype. This study conducted a systematic review with an emphasis on epidemiological and prognostic factors based on the molecular classification proposed by TCGA.

Methods: A broad, comprehensive, and reproducible search with methodological rigor was conducted for study selection using the ROBINS-I and GRADEpro protocols and appropriate combinations of keywords.

Results: A total of 25 studies were selected: six with a complete classification similar to TCGA and 19 with a distinction between MSI-H and EBV+. The application of meta-analysis calculations reinforces the prevalence of positive Epstein-Barr adenocarcinomas in males and high microsatellite instability in females, with a high level of certainty of evidence and low risk of bias in the analyzed studies due to the rigorous methods used.

Conclusion: The molecular classification proposed by TCGA shows limited dissemination, with MSI-H and EBV+ subtypes being the most researched, probably due to the benefit of the association with immunotherapies. However, the subclassification cannot be restricted to less than a quarter of the cases, and improvements in this aspect are urgent for the construction of knowledge on this important topic of global health.

Keywords: EBV+ adenocarcinoma; MSI‐H adenocarcinoma; gastric adenocarcinoma; molecular classification; systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adenocarcinoma* / epidemiology
  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / epidemiology
  • Epstein-Barr Virus Infections* / genetics
  • Female
  • Herpesvirus 4, Human / genetics
  • Humans
  • Male
  • Microsatellite Instability
  • Microsatellite Repeats
  • Stomach Neoplasms* / epidemiology
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology