Analysis of epigenetic regulation in the diversity of hepatocellular carcinoma

• Project/Area Number: 18K07900
• 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: The University of Tokyo
• Principal Investigator: Minami Tatsuya 東京大学, 医学部附属病院, 助教 (60459401)
• Co-Investigator(Kenkyū-buntansha): 立石 敬介 東京大学, 医学部附属病院, 講師 (20396948) ; 中塚 拓馬 東京大学, 医学部附属病院, 助教 (50772042)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 肝癌 / 肝がん / 肝臓がん

Outline of Final Research Achievements

The mechanisms of tumor herterogeneity remain to be elucidated. Hepatocellular carcinoma sometimes represent mixed subtype including cholangiocarcinoma tissues. This research project aims to address the significance of IDH mutation in the development of heterogeneity in liver cancers.

Academic Significance and Societal Importance of the Research Achievements

本研究では肝がんの発生や進展における分化異常に対するIDH変異の影響について、遺伝子改変マウスおよび肝がん幹細胞の解析、さらには臨床検体を用いた検討を行い、臨床的マーカーとしての可能性も検証する。IDH変異が肝がん幹細胞のレベルにおける分化制御に及ぼす影響を解析できる点で学術的意義が高い。さらにIDH遺伝子変異については、すでに変異特異的な阻害化合物の開発もなされていることも併せ、将来的には特異的分子標的治療および診断法の開発に直結する創造性も有している。

Research Products

• [Journal Article] Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis (2021)
  • Author(s): Sapena V, Enea M, Torres F, Celsa C, Rios J, Rizzo GEM, Nahon P, Marino Z, Tateishi R, Minami T, Sangiovanni A, Forns X, Toyoda H, Brillanti S, Conti F, Degasperi E, Yu ML, Tsai PC, Jean K, El Kassas M, Shousha HI, Omar A, Zavaglia C, Nagata H, Nakagawa M, Asahina Y, et al
  • Journal Title: Gut Volume: in press Issue: 3 Pages: 323663-323663
  • DOI: 10.1136/gutjnl-2020-323663
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Post-treatment cell-free DNA as a predictive biomarker in molecular-targeted therapy of hepatocellular carcinoma (2021)
  • Author(s): Nakatsuka T、Nakagawa H、Hayata Y、Wake T、Yamada T、Nishibatake Kinoshita M、Nakagmi R、Sato M、Minami T、Uchino K、Enooku K、Kudo Y、Tanaka Y、Kishikawa T、Otsuka M、Tateishi R、Koike K
  • Journal Title: Journal of Gastroenterology Volume: - Issue: 5 Pages: 01773-4
  • DOI: 10.1007/s00535-021-01773-4
  • Peer Reviewed
• [Journal Article] Chronological change in alpha‐fetoprotein levels in hepatocellular carcinoma after eradication of hepatitis C virus (2020)
  • Author(s): Fukumoto Tsuyoshi、Minami Tatsuya、Tateishi Ryosuke、Koike Kazuhiko
  • Journal Title: Liver International Volume: 40 Issue: 9 Pages: 2305-2306
  • DOI: 10.1111/liv.14544
• [Journal Article] Mutant IDH1 confers resistance to energy stress in normal biliary cells through PFKP-induced aerobic glycolysis and AMPK activation (2019)
  • Author(s): Fujiwara H、Tateishi K、Misumi K、Hayashi A、Igarashi K、Kato H、Nakatsuka T、Suzuki N、Yamamoto K、Kudo Y、Hayakawa Y、Nakagawa 、Tanaka Y、Ijichi H、Kogure H、Nakai Y、Isayama H、Hasegawa K、Fukayama M、Soga T、Koike K
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 18859-18859
  • DOI: 10.1038/s41598-019-55211-w
  • Peer Reviewed / Open Access