Clinicopathological evidence of hepatitis B virus infection in the development of gastric adenocarcinoma

J Med Virol. 2020 Jan;92(1):71-77. doi: 10.1002/jmv.25584. Epub 2019 Sep 10.

Abstract

Gastric cancer (GC) is one of the infection-related cancers. Helicobacter pylori and Epstein-Barr virus (EBV) were established risk factors for GC. Recently, there are several reports showing the inconsistent association between hepatitis B virus (HBV) infection and the development of GC. To explore the relationship between HBV infection and the development of GC, we designed a meta-analysis of previous epidemiological studies, a hospital-based case-control study, followed by an immunohistochemistry (IHC) assay of HBV-exposed GC samples. We found that HBV infection was associated with an increased risk of GC based on the meta-analysis. No significant association between HBV infection and GC was detected according to our hospital-based case-control study. Histological examination showed that the gastric epithelium positive for HBx demonstrated a higher nuclear-cytoplasmic ratio compared to those HBx-negative cells. HBx and HBcAg were expressed more in tumors than those in normal counterparts in HBV-exposed subjects, and PD-L1 was lower in GC tissues from HBV carriers than those in HBV clearances. In conclusion, HBV infection may contribute to a higher risk for GC based on the meta-analysis and to the morphological atypia of gastric epithelium by the histological assessment, and GC patients among HBV carriers showed lower expression of PD-L1 may lose the chance for immune checkpoint blockade therapy.

Keywords: PD-L1; gastric cancer; hepatitis B virus.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / virology*
  • Aged
  • B7-H1 Antigen / genetics
  • Case-Control Studies
  • Female
  • Gastric Mucosa / pathology
  • Gastric Mucosa / virology*
  • Hepatitis B / complications*
  • Hepatitis B Core Antigens / genetics
  • Hepatitis B virus / pathogenicity
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Stomach Neoplasms / virology*
  • Trans-Activators / genetics
  • Viral Regulatory and Accessory Proteins / genetics

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Hepatitis B Core Antigens
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein