Severe Induction of Aberrant DNA Methylation by Nodular Gastritis in Adults

Overview

Journal J Gastroenterol

Specialty Gastroenterology

Date 2024 Mar 19

PMID 38499886

Authors

Akiko Sasaki

Hideyuki Takeshima

Satoshi Yamashita

Chikamasa Ichita

Jun Kawachi

Wataru Naito

Yui Ohashi

Chihiro Takeuchi

Masahide Fukuda

Yumi Furuichi

Nobutake Yamamichi

Takayuki Ando

Hideki Kobara

Tohru Kotera

Takao Itoi

Chihiro Sumida

Akinobu Hamada

Kazuya Koizumi

Toshikazu Ushijima

Affiliations

Soon will be listed here.

Abstract

Background: Nodular gastritis (NG) is characterized by marked antral lymphoid follicle formation, and is a strong risk factor for diffuse-type gastric cancer in adults. However, it is unknown whether aberrant DNA methylation, which is induced by atrophic gastritis (AG) and is a risk for gastric cancer, is induced by NG. Here, we analyzed methylation induction by NG.

Methods: Gastric mucosal samples were obtained from non-cancerous antral tissues of 16 NG and 20 AG patients with gastric cancer and 5 NG and 6 AG patients without, all age- and gender-matched. Genome-wide methylation analysis and expression analysis were conducted by a BeadChip array and RNA-sequencing, respectively.

Results: Clustering analysis of non-cancerous antral tissues of NG and AG patients with gastric cancer was conducted using methylation levels of 585 promoter CpG islands (CGIs) of methylation-resistant genes, and a large fraction of NG samples formed a cluster with strong methylation induction. Promoter CGIs of CDH1 and DAPK1 tumor-suppressor genes were more methylated in NG than in AG. Notably, methylation levels of these genes were also higher in the antrum of NG patients without cancer. Genes related to lymphoid follicle formation, such as CXCL13/CXCR5 and CXCL12/CXCR4, had higher expression in NG, and genes involved in DNA demethylation TET2 and IDH1, had only half the expression in NG.

Conclusions: Severe aberrant methylation, involving multiple tumor-suppressor genes, was induced in the gastric antrum and body of patients with NG, in accordance with their high gastric cancer risk.

Citing Articles

Chen Y, Zou Q, Chen Q, Wang S, Du Q, Mai Q Heliyon. 2024; 10(17):e36240.

PMID: 39263148 PMC: 11387271. DOI: 10.1016/j.heliyon.2024.e36240.

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