2018 Fiscal Year Final Research Report

DNA methylation level of 10 CpG sites on 8 specific genes in non-cancerous liver tissues is useful to predict multicentric recurrence of hepatocellular carcinoma after surgical resection

Research Project

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Project/Area Number	16K09385
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Gastroenterology
Research Institution	Kurume University
Principal Investigator	Torimura Takuji 久留米大学, 医学部, 教授 (60197986)
Co-Investigator(Kenkyū-buntansha)	中村徹久留米大学, 医学部, 講師 (30341332) 矢野博久久留米大学, 医学部, 教授 (40220206) 岩本英希久留米大学, 医学部, 助教 (40529541) 山本健久留米大学, 医学部, 教授 (60274528)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	肝細胞癌 / 多中心性再発 / DNAメチル化異常 / 非癌部肝組織
Outline of Final Research Achievements	The mechanism of multicentric recurrence after curative treatment of hepatocellular carcinoma (HCC) is not clarified yet. The aim of this study is to clarify the participation of DNA methylation in multicentric recurrence of HCC and also evaluate the possibility of DNA methylation as a biomarker of multicentric recurrence.26 HCC patients recurred multicentrically within 2 years after surgical resection (early recurrence group) and 22 HCC patients without recurrence more than 5 years (no recurrence group) were enrolled. Between 1st and 2nd sets, 10 common DNA methylation sites which showed significantly different methylation level (p<0.001) were identified on 8 genes. 9 sites of 10 common DNA methylation sites showed hypomethylation level in early recurrence group. After curative resection of HCC, the DNA methylation level in non-cancerous liver tissues seems to be a biomarker of multicentric recurrence of HCC.
Free Research Field	肝臓病学
Academic Significance and Societal Importance of the Research Achievements	本研究は肝細胞癌の多中心性再発予測を可能にすることを目指した研究である。無再発群と早期再発群のDNAメチル化レベルの差を検定した結果両群間で差を認める部位を8遺伝子領域10箇所に同定した。これら10箇所のメチル化レベルを用いた分析により、無再発群と早期再発群の識別が可能であった。8遺伝子には転写因子、シグナル伝達分子、細胞増殖関連分子などが含まれていた。以上から、同定した非癌部肝組織のDNAメチル化領域のメチル化レベルは肝細胞癌の根治切除後の多中心性再発を予測する有用なマーカーになり得ること。さらにその領域に位置する遺伝子群は、多中心性再発の原因の遺伝子候補となり得ることが示唆された。