MicroRNAs as early predictors of efficacy and drug resistance to molecularly targeted therapy in hepatocellular carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15928
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kagawa University
• Principal Investigator: Oura Kyoko 香川大学, 医学部附属病院, 助教 (80834639)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肝細胞癌 / microRNA / atezolizumab / bevacizumab

Outline of Final Research Achievements

Sixty-six patients with uHCC treated with Atezo/Bev were included. Comparing 44 patients in the response group with 22 patients in the non-response group, 10 miRNAs were significantly elevated before treatment in the response group, especially miR-485-3p, which was higher than in the non-response group and further elevated on the next day and 3 weeks later. Serum VEGF levels before treatment were not significantly different, but both groups decreased to below detection sensitivity the next day, and the 3-week/pre-treatment ratio was significantly lower in the response group than in the non-response group. In vitro, miR-485-3p transfection suppressed migration and proliferation in HuH-7, enhanced PIAS3 expression, and suppressed STAT3/VEGF expression, which were more pronounced in cells co-cultured with HuVEC.

Free Research Field

肝臓病

Academic Significance and Societal Importance of the Research Achievements

Atezo/Beva併用療法において、血清miR-485-3pはVEGFより鋭敏に変化するため、早期治療効果を予測するのに有用である。PIAS3/STAT3/VEGF signalが関連しており、今後バイオマーカーや創薬開発に臨床応用できる可能性がある。