Elucidation of therapeutic response mechanisms in liver cancer by integrated genomic analysis using nucleic acids in peripheral blood

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17392
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Murakawa Miyako 東京医科歯科大学, 医学部附属病院, 助教 (20733851)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 肝細胞癌 / 遺伝子変異 / 肝炎ウイルス

Outline of Final Research Achievements

We investigated the patterns of genetic changes characteristic of the cancer using surgical and blood specimens obtained from the patients treated for hepatocellular carcinoma. In particular, we analyzed the characteristics of hepatocellular carcinoma, which occurs despite viral control, and found that it has genomic mutations that are different from those under viral control and that carcinogenesis is also affected by liver fibrosis and inflammation, alcohol consumption, and diabetes. In addition, we confirmed that it is possible to evaluate the genomic characteristics of hepatocellular carcinoma, including TERT mutation, by analyzing DNA present in very small amounts in blood, and established a basis for analyzing genomic changes associated with the effects of anti-cancer agents on inoperable advanced cancer.

Free Research Field

肝臓病

Academic Significance and Societal Importance of the Research Achievements

今回の研究では抗がん剤の治療効果に直結する肝癌遺伝子変化の同定には至らなかったが、Liquid biopsyにより肝癌の遺伝子解析が可能であることを示した点は、新規治療薬が承認され治療選択肢が広がっている現状において手術不能肝癌の最適な治療選択に向けた特徴の解明、新たな分類の可能性につながる。また、ウイルス制御下や非ウイルス性肝癌は手術不能な進行癌で発見される症例も多いが、臨床データベースを用いて肝癌の臨床的特徴とゲノム変化の関連を解析する中でFIB4-indexがウイルス制御下発癌の高リスク群の囲い込みに有用であることを見出したことは、効率的な癌サーベイランスに向けて社会的意義が大きい。