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19.03.2024 | Original Article—Alimentary Tract

Severe induction of aberrant DNA methylation by nodular gastritis in adults

verfasst von: 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

Erschienen in: Journal of Gastroenterology

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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.

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Titel: Severe induction of aberrant DNA methylation by nodular gastritis in adults
verfasst von: 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
Publikationsdatum: 19.03.2024
Verlag: Springer Nature Singapore
Erschienen in: Journal of Gastroenterology
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI: https://doi.org/10.1007/s00535-024-02094-y

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