Severe induction of aberrant DNA methylation by nodular gastritis in adults

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*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

3 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)442-456
ページ数15
ジャーナルJournal of Gastroenterology
59
6
DOI
出版ステータス出版済み - 2024/06

ASJC Scopus 主題領域

  • 消化器病学

フィンガープリント

「Severe induction of aberrant DNA methylation by nodular gastritis in adults」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル