Development of a Personalized Hepatocellular Carcinoma Risk Prediction Model for Chronic Liver Disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20910
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0903:Organ-based internal medicine and related fields
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: kaneko Shun 東京医科歯科大学, 東京医科歯科大学病院, 助教 (60801959)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 肝細胞癌 / B型肝炎ウイルス / 慢性肝疾患

Outline of Final Research Achievements

A multivariate analysis with chronic hepatitis B (CHB) patients revealed that gender, older age, lower platelet counts at the baseline and liver stiffness measurement (LSM) levels significantly associated with hepatocellular carcinoma (HCC) development from our clinical database. The LSM was a most valuable for a stratification. It suggests that any time LSM but not CAP might yield better surveillance for CHB patients.
As basic analysis, we focused on that KMT2B is the second most frequent locus of HBV-DNA integration in HCC. To elucidate the oncogenic mechanism, we identified the HBV integrated sequence from the HCC specimen with HBV-KMT2B integration and reproduced the integration in human induced pluripotent stem cells. From analysis for the functional significance of HBV-KMT2B integration in HBV-associated HCC by differentiating them into hepatic lineages, HBV-KMT2B integration involved oncogenic processes of normal hepatocytes.

Free Research Field

肝細胞癌

Academic Significance and Societal Importance of the Research Achievements

本研究成果からB型慢性肝疾患の肝発癌においては、男性、年齢、血小板数、肝硬度といった宿主因子を主とした因子が抽出されること、既存のHBV検査項目では検知できない因子がありうることについても示唆され、その社会的意義は大きいと考えられた。
また肝発癌機序として、宿主肝細胞にHBVゲノムが組込まれることがあるが、今回の基礎的検討によって、機能的意義が不明であったKMT2B- HBV integrationによる肝発癌機構解明を進めることにより、HBV肝発癌の病態解明、及び慢性肝疾患の進展を阻止しうる個人差を踏まえた精緻医療開発へ向けた学術・技術的な基盤形成に貢献すると考えられ、学術的意義は大きい。