Role of regeneration nodule in cirrhotic liver on tumorigenesis

• Project/Area Number: 17H04158
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: Marusawa Hiroyuki 京都大学, 医学研究科, 客員研究員 (80324630)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000); Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
• Keywords: 肝癌 / 肝硬変 / 遺伝子異常 / 癌 / ゲノム / ウィルス

Outline of Final Research Achievements

Hepatocellular carcinoma recurrently develops in cirrhotic liver containing a number of regenerative nodules (RNs). To uncover the molecular basis of tumorigenesis in liver cirrhosis, the genetic aberrations in RNs of cirrhotic tissues were determined using next-generation sequencing method. Our findings suggested that a variety of genetic aberrations accmulate in the RNs of cirrhotic liver before the development of clinically and histologically overt HCC, and these aberrations in RNs could provide the basis of tumorigenesis in patients with liver cirrhosis.

Academic Significance and Societal Importance of the Research Achievements

本邦でも頻度の高い癌のひとつである肝癌は肝硬変を背景に高率に発生することが知られている。この肝硬変は、肝臓の線維化と再生結節と呼ばれる肝細胞の構成単位により形成されているが、本研究により肝硬変の再生結節に遺伝子異常が蓄積することが、肝癌の発生母地となっていることがわかってきた。

Research Products

• [Journal Article] Comprehensive analysis of genetic aberrations linked to tumorigenesis in regenerative nodules of liver cirrhosis (2019)
  • Author(s): Kim Soo Ki、Takeda Haruhiko、Takai Atsushi、Matsumoto Tomonori、Kakiuchi Nobuyuki、Yokoyama Akira、Yoshida Kenichi、Kaido Toshimi、Uemoto Shinji、Minamiguchi Sachiko、Haga Hironori、Shiraishi Yuichi、Miyano Satoru、Seno Hiroshi、Ogawa Seishi、Marusawa Hiroyuki
  • Journal Title: Journal of Gastroenterology Volume: 印刷中 Issue: 7 Pages: 628-640
  • DOI: 10.1007/s00535-019-01555-z
  • Peer Reviewed / Open Access
• [Journal Article] Proliferating EpCAM-Positive Ductal Cells in the Inflamed Liver Give Rise to Hepatocellular Carcinoma (2017)
  • Author(s): Matsumoto Tomonori、Takai Atsushi、Eso Yuji、Kinoshita Kazuo、Manabe Toshiaki、Seno Hiroshi、Chiba Tsutomu、Marusawa Hiroyuki
  • Journal Title: Cancer Research Volume: 77 Issue: 22 Pages: 6131-6143
  • DOI: 10.1158/0008-5472.can-17-1800
  • Peer Reviewed
• [Presentation] Oncogenic Potential of Cirrhotic Liver Tissues Determined by Deep-Sequencing Analyses. (2018)
  • Author(s): Soo Ki Kim , Haruhiko Takeda , Hiroyuki Marusawa.
  • Organizer: APASL 2018
  • Int'l Joint Research
• [Presentation] 肝がんのゲノム情報に基づく成因別治療選択の可能性 (2018)
  • Author(s): 金 秀基，竹田治彦，丸澤宏之
  • Organizer: 第54回日本肝臓学会総会
• [Presentation] 起源細胞の違いに基づいた肝癌の腫瘍特性の同定 (2017)
  • Author(s): 松本知訓、高井淳、恵荘裕嗣、木下和生、千葉勉、妹尾浩、丸澤宏之
  • Organizer: 第76回日本癌学会学術総会