Highly Sensitive Detection for HBV Driver Mutations and Construction of a PRS Model

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07997
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical and Dental University (2023); National Center for Global Health and Medicine (2021-2022)
• Principal Investigator: Nishida Nao 東京医科歯科大学, 難治疾患研究所, 准教授 (50456109)
• Co-Investigator(Kenkyū-buntansha): 大橋 順 東京大学, 大学院理学系研究科(理学部), 教授 (80301141) ; 吉住 朋晴 九州大学, 医学研究院, 教授 (80363373)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ターゲットキャプチャーシークエンシング / B型肝炎 / 体細胞変異

Outline of Final Research Achievements

The cancer genome analysis pipeline for detecting the mutation which existed in the liver cancer tissue at the low frequency was constructed. Targeted capture sequencing was performed on DNA extracted from 182 liver cancer tissue samples collected during the study period, and low-frequency mutations are currently being analyzed.
Liver tissue samples of all 672 hepatitis B patients were newly collected from collaborating institutes, and a model was constructed to predict the number of days until liver cancer developed. ROC analysis using cumulative probability of developing liver cancer (One year, three years from now.) showed that the model including 4 items (Blood test Age, sex, presence/absence of Log10AFP, HLA-A*33:03) had AUC=0.862 and 0.863, respectively.

Free Research Field

ゲノム解析

Academic Significance and Societal Importance of the Research Achievements

本研究において、ディープシークエンスにより肝がんドライバー変異を高感度に検出する測定系を開発した。リキッドバイオプシーや肝生検試料の中に微量に存在する肝がんドライバー変異を高感度かつ高精度に検出することが可能となれば、B型慢性肝炎患者の中で肝がんを発症するリスクの高い患者を囲い込むことが可能となる。治療が必要な患者を選択することで適切な治療や投薬を行うことが可能になると期待される。