Analysis of the genome wide epigenetic aberration in the esophagogastric junction cancer carcinogenesis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Jichi Medical University
• Principal Investigator: Saito Masaaki 自治医科大学, 医学部, 講師 (00382911)
• Co-Investigator(Kenkyū-buntansha): 鈴木 浩一 自治医科大学, 医学部, 教授 (70332369) ; 力山 敏樹 自治医科大学, 医学部, 教授 (80343060)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 食道胃接合部癌 / エピジェネティック異常 / H. Pylori陰性胃癌

Outline of Final Research Achievements

In this study, we hypothesized that chronic inflammation caused by exposure to gastric acid and bile acid induces demethylation, one of the epigenome abnormalities, and induces chromosomal instability during the carcinogenesis process of Barrett's esophageal adenocarcinoma.
In patients with Barrett's esophageal carcinoma, demethylation levels of Satellite alpha (SAT) were found to be significantly higher in the adenocarcinoma than in the background mucosa. In addition, when we examined the induction of chromosomal instability by acid and bile acid exposure, chromosomal instability was observed in the Barrett esophageal cell line, which showed upregulation of SAT. From the above, we clarified that acid and bile acid exposure may be involved in the carcinogenesis process of Barrett's esophageal adenocarcinoma.

Free Research Field

消化器癌発癌

Academic Significance and Societal Importance of the Research Achievements

本研究では、胃酸および胆汁酸への曝露が、Barrett上皮細胞株においてセントロメア領域での DNA脱メチル化を促進し、染色体不安定性を引き起こすことを初めて報告した。本研究は、バレット食道に由来する食道胃接合部癌の発生メカニズムに解明するうえで重要と考えられる。また、セントロメア領域での DNA脱メチル化とバレット食道との関連の検討は新たなバイオマーカーとしての活用やBarrett食道患者でのサーベイランス間隔の決定への一助となる可能性があり、今後の研究課題となりうる。