TY - JOUR
T1 - Severe induction of aberrant DNA methylation by nodular gastritis in adults
AU - Sasaki, Akiko
AU - Takeshima, Hideyuki
AU - Yamashita, Satoshi
AU - Ichita, Chikamasa
AU - Kawachi, Jun
AU - Naito, Wataru
AU - Ohashi, Yui
AU - Takeuchi, Chihiro
AU - Fukuda, Masahide
AU - Furuichi, Yumi
AU - Yamamichi, Nobutake
AU - Ando, Takayuki
AU - Kobara, Hideki
AU - Kotera, Tohru
AU - Itoi, Takao
AU - Sumida, Chihiro
AU - Hamada, Akinobu
AU - Koizumi, Kazuya
AU - Ushijima, Toshikazu
N1 - Publisher Copyright:
© Japanese Society of Gastroenterology 2024.
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
KW - Chronic inflammation
KW - Epigenetics
KW - Helicobacter pylori
KW - Molecular epidemiology
UR - http://www.scopus.com/inward/record.url?scp=85188128230&partnerID=8YFLogxK
U2 - 10.1007/s00535-024-02094-y
DO - 10.1007/s00535-024-02094-y
M3 - 学術論文
C2 - 38499886
AN - SCOPUS:85188128230
SN - 0944-1174
VL - 59
SP - 442
EP - 456
JO - Journal of Gastroenterology
JF - Journal of Gastroenterology
IS - 6
ER -