Helicobacter pylori infection associated DNA methylation in primary gastric cancer significantly correlates with specific molecular and clinicopathological features

Sayumi Tahara, Tomomitsu Tahara, Jumpei Yamazaki, Takuya Shijimaya, Noriyuki Horiguchi, Kohei Funasaka, Toshiro Fukui, Yoshihito Nakagawa, Tomoyuki Shibata, Makoto Naganuma, Tetsuya Tsukamoto, Naoki Ohmiya

Research output: Contribution to journalArticlepeer-review

Abstract

Helicobacter pylori induces DNA methylation in gastric mucosa, which links to gastric cancer (GC) risk. In contrast, CpG island methylator phenotype (CIMP) is defined as high levels of cancer-specific methylation and provides distinct molecular and clinicopathological features of GC. The association between those two types of methylation in GC remains unclear. We examined DNA methylation of well-validated H. pylori infection associated genes in GC and its adjacent mucosa and investigated its association with CIMP, various molecular subtypes and clinical features. We studied 50 candidate loci in 24 gastric samples to identify H. pylori infection associated genes. Identified loci were further examined in 624 gastric tissue from 217 primary GC, 217 adjacent mucosa, and 190 mucosae from cancer-free subjects. We identified five genes (IGF2, SLC16A2, SOX11, P2RX7, and MYOD1) as hypermethylated in H. pylori infected gastric mucosa. In non-neoplastic mucosa, methylation of H. pylori infection associated genes was higher in patients with GC than those without. In primary GC tissues, higher methylation of H. pylori infection associated genes correlated with CIMP-positive and its related features, such as MLH1 methylated cases. On the other hand, GC with lower methylation of these genes presented aggressive clinicopathological features including undifferentiated histopathology, advanced stage at diagnosis. H. pylori infection associated DNA methylation is correlated with CIMP, specific molecular and clinicopathological features in GC, supporting its utility as promising biomarker in this tumor type.

Original languageEnglish
Pages (from-to)266-274
Number of pages9
JournalMolecular Carcinogenesis
Volume63
Issue number2
DOIs
Publication statusPublished - 02-2024

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

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