Severe induction of aberrant DNA methylation by nodular gastritis in adults

被引：3

作者：

Sasaki, Akiko ^{[1
,2
]}

Takeshima, Hideyuki ^{[1
,3
]}

Yamashita, Satoshi ^{[1
]}

Ichita, Chikamasa ^{[2
]}

Kawachi, Jun ^{[4
]}

Naito, Wataru ^{[5
]}

Ohashi, Yui ^{[3
]}

Takeuchi, Chihiro ^{[1
,3
]}

Fukuda, Masahide ^{[1
,6
]}

Furuichi, Yumi ^{[1
,3
,7
]}

Yamamichi, Nobutake ^{[8
]}

Ando, Takayuki ^{[9
]}

Kobara, Hideki ^{[10
]}

Kotera, Tohru ^{[11
]}

Itoi, Takao ^{[12
]}

Sumida, Chihiro ^{[2
]}

Hamada, Akinobu ^{[13
]}

Koizumi, Kazuya ^{[2
]}

Ushijima, Toshikazu ^{[1
,3
]}

机构：

[1] Natl Canc Ctr, Res Inst, Div Epigen, Tokyo, Japan

[2] Shonan Kamakura Gen Hosp, Gastroenterol Med Ctr, Kamakura, Kanagawa, Japan

[3] Hoshi Univ, Inst Adv Life Sci, Dept Epigen, Tokyo, Japan

[4] Shonan Kamakura Gen Hosp, Dept Gen Surg, Kanagawa, Japan

[5] Shonan Kamakura Gen Hosp, Dept Diagnost Pathol, Kamakura, Kanagawa, Japan

[6] Oita Univ, Fac Med, Dept Gastroenterol, Oita, Japan

[7] Kagawa Univ, Fac Med, Dept Gastroenterol Surg, Kagawa, Japan

[8] Univ Tokyo, Ctr Epidemiol & Prevent Med, Grad Sch Med, Tokyo 1138655, Japan

[9] Univ Toyama, Dept Internal Med 3, Toyama, Japan

[10] Kagawa Univ, Dept Gastroenterol & Neurol, Kagawa, Japan

[11] Uji Tokushukai Med Ctr, Dept Med Examinat, Kyoto, Japan

[12] Tokyo Med Univ, Dept Gastroenterol & Hepatol, Tokyo, Japan

[13] Natl Canc Ctr, Res Inst, Div Mol Pharmacol, Tokyo, Japan

来源：

JOURNAL OF GASTROENTEROLOGY | 2024年 / 59卷 / 06期

关键词：

Chronic inflammation; Helicobacter pylori; Epigenetics; Molecular epidemiology; HELICOBACTER-PYLORI INFECTION; CANCER-RISK; ASSOCIATION; HYPERMETHYLATION; PROMOTER;

D O I：

10.1007/s00535-024-02094-y

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BackgroundNodular 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.MethodsGastric 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.ResultsClustering 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.ConclusionsSevere 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.

引用

页码：442 / 456

页数：15

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