Elucidation of mechanisms underlying gastric cancer development by epigenetic analysis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Keio University
• Principal Investigator: Matano Mami 慶應義塾大学, 医学部(信濃町), 特任助教 (20439889)
• Co-Investigator(Kenkyū-buntansha): 南木 康作 慶應義塾大学, 医学部(信濃町), 助教 (30571137) ; 佐藤 俊朗 慶應義塾大学, 医学部(信濃町), 教授 (70365245)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胃がん / オルガノイド / エピゲノム / CRISPR-Cas9

Outline of Final Research Achievements

Recently, epigenetic mechanisms underlying gastric cancer development are highlighted. However, detailed molecular basis has not been fully elucidated. In this study, we aimed to reveal epigenetic mechanisms that contribute to malignant transformation and develop targeted therapies using organoid technology.
Comprehensive epigenetic analysis of a gastric cancer organoid library revealed that there is a subtype characterized by loss of activity of transcription factors characteristic of intestinal tracts and gain of activity of different types of transcription factors. This subtype had a particularly poor prognosis. To explore targeted therapies for this subtype, we conducted CRISPR-based knockout screening targeting epigenetic regulatory proteins. We are currently trying to identify proteins that can be targeted specifically to this subtype for therapeutic development.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は，胃がんのエピゲノム異常という観点から新たな治療標的の可能性を探る研究である．胃がん発症・悪性化に関与する環境因子や分子遺伝学的変化を理解し，前がん病変を防ぐ予防医学や，がんの悪性化機構を阻害する新しい治療戦略の開発が期待される．
また本研究は，ヒト細胞を用いたエピゲノム異常による腫瘍進行の機序解明を図る技術基盤となりうるとともに，臨床疾患サンプルの純度，精度の高いエピジェネティクスデータとして，貴重なリソースとなり，臨床・研究・産業に与える影響は大きいと考えられる．