2014 Fiscal Year Final Research Report
Identification of risk factors of hepatocarcinogenesis in fatty liver disease through the comprehensive analysis of epigenetic alterations
| Project/Area Number |
24590997
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kinki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HATANO Etsurou 京都大学, 大学院医学研究科, 准教授 (80359801)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 脂肪性肝疾患 / 肝細胞癌 / エピジェネティクス / がん抑制遺伝子 |
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| Outline of Final Research Achievements |
We found that oxidative DAN damage (8-OHdG) induced epigenetic alteration in HCC cell lines. In human chronic hepatitis C, number of methylated tumor suppressor genes (TSGs) was associated with time-to hepatocellular carcinoma (HCC) emergence. Through the comprehensive analysis of DNA methylation in virus-negative HCCs, methylation was affected by aging and presence of diabetes mellitus (DM), suggesting that age and DM might contribute to hepatocarcinogenesis through epigenetic mechanism. We analyzed risk factors of fatty liver-related HCC mergence using 8-OHdG level of hepatocyte as a surrogate marker, and found that serum AFP and hepatocyte ballooning were independently associated with 8-OHdG; number of methylated TSGs was significantly higher in livers with high degree of 8-OHdG levels in hepatocyte. These evidences support the idea that serum AFP level and hepatocyte ballooning could be a marker of high-risk group of HCC in patients with fatty liver.
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| Free Research Field |
消化器内科
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