Epigenetics of combined hepatocellular-cholangiocarcinoma

• Project/Area Number: 18K15106
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Kurume University
• Principal Investigator: Kusano Hironori 久留米大学, 医学部, 講師 (30569380)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝がん / エピジェネティクス / EZH2 / H3K27me3 / p16 / 混合型肝癌

Outline of Final Research Achievements

Methylation of lysine 27 on histone H3 (H3K27) and gene silencing of p16 by the EZH2 complex are an epigenetic mechanism in cancer progression. In this study we evaluated the immunohistochemical expression of EZH2, H3K27me3, and p16 in intrahepatic cholangiocarcinoma (iCCA) and intermediate cell carcinoma of the liver (ICL). EZH2, H3K27me3, and p16 were expressed in 71%, 73%, and 34% of iCCA cases, and in 63%, 54%, and 24% of ICL cases respectively. EZH2 and H3K27me3 expressions were positively correlated in both iCCA and ICL cases. There was no correlation between prognosis and the expression status of EZH2, H3K27me3, or p16.

Academic Significance and Societal Importance of the Research Achievements

がんの発生・増殖・進展においては遺伝子異常のみならず、エピジェネティックな異常が重要であることが知られている。本研究ではエピジェネティクスに関連したEZH2, H3K27me3, p16と呼ばれるタンパクの発現を難治性がんである肝がんにおいて検討した。EZH2とH3K27me3の発現に関連が相関があることがわかった。この結果から肝がんにおいてもエピジェネティックな異常の関与が示唆された。一方これらのタンパクの発現と予後に直接の関連が無いこともわかった。

Research Products

• [Journal Article] Distinctive clinicopathological features and KRAS and IDH1/2 mutation status of cholangiolocellular carcinoma. (2020)
  • Author(s): Hironori Kusano
  • Journal Title: Hepatol Res Volume: 50 Issue: 1 Pages: 84-91
  • DOI: 10.1111/hepr.13428
  • Peer Reviewed
• [Journal Article] Malic enzyme 1 is a potential marker of combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell type. (2019)
  • Author(s): Mihara Y, Akiba J, Ogasawara S, Kondo R, Fukushima H, Itadani H, Obara H, Kakuma T, Kusano H, Naito Y, Okuda K, Nakashima O, Yano H.
  • Journal Title: Hepatology Research Volume: 印刷中 Issue: 9 Pages: 1066-1075
  • DOI: 10.1111/hepr.13365
  • Peer Reviewed
• [Journal Article] Programmed death-ligand 1 expression is an unfavorable prognostic factor of hepatocellular carcinoma after archiving sustained virologic response for hepatitis C virus infection. (2019)
  • Author(s): Reiichiro Kondo
  • Journal Title: Oncol Lett Volume: 18 Pages: 1458-1466
  • DOI: 10.3892/ol.2019.10448
  • Peer Reviewed / Open Access
• [Journal Article] Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo. (2019)
  • Author(s): Sachiko Ogasawara
  • Journal Title: Anticancer Res Volume: 39 Issue: 11 Pages: 5973-5982
  • DOI: 10.21873/anticanres.13802
  • Peer Reviewed
• [Presentation] Clinicopathologic characteristics of scirrhous hepatocellular carcinomas with or without steatohepatitic features (2020)
  • Author(s): Hironori Kusano
  • Organizer: USCAP 109th annual meeting
  • Int'l Joint Research
• [Presentation] 混合型肝癌中間型の組織像と新規マーカーの検索 (2019)
  • Author(s): 草野弘宣
  • Organizer: 第55回日本肝癌研究会
• [Presentation] Malic enzyme 1（ME1）は混合型肝癌中間細胞亜型の診断マーカーとして有用である. (2019)
  • Author(s): 三原勇太郎、秋葉 純、小笠原幸子、近藤礼一郎、福嶋 浩人、 板谷 啓、草野 弘宣、内藤 嘉紀、中島 収、矢野 博久
  • Organizer: 第108 回日本病理学会総会