A miRNA signature as a diagnostic biomarker for microvascular invasion in hepatocellular carcinoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15596
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kumamoto University
• Principal Investigator: Yamamura Kensuke 熊本大学, 大学院生命科学研究部(医), 特定研究員 (10816507)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 肝細胞癌 / 微少脈管侵襲 / マイクロRNA / バイオマーカー / signature

Outline of Final Research Achievements

We initially identified a 16-gene expression signature from a total of 19245 genes, which showed significant predictive power for recurrence free survival (RFS) in non B non C HCC patients [HR: 5.02 (3.12 - 8.08), p<0.0001]. Subsequently, using clinical training cohort, we developed a reduced and optimized 4 gene signature composed of DKK1, CTSL2, MAMSTR and HLA-G, which demonstrated as a robust model in predicting RFS (HR, 3.05; 95%CI, 1.81 - 5.14; P<0.0001). The performance of the gene signature was validated in two independent clinical cohorts (HR, 3.39; 95% CI: 1.98 - 5.79, P<0.0001 and HR, 3.44; 95%CI: 1.95 - 6.06, P<0.0001). Furthermore, a nomogram comprising our four gene signature, tumor size, number of tumors, AFP, and DCP was generated to predict the 2-year recurrence free survival in the training cohort, and it performed well in the two independent validation cohorts (concordance index: 0.73 and 0.71, respectively).

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

システマティックかつ網羅的なバイオマーカーの探索及び検証を行うことで、NBNC-HCCの再発予測ノモグラムを樹立した。個々の患者の再発予測に有用な臨床ツールとなりうる。