Abstract 4017: Integrated multi-omics approaches in resectable hepatocellular carcinoma with microvascular invasion for revealing therapeutic target

Abstract Introduction: Hepatocellular carcinoma(HCC) with microvascular invasion(MVI) has the traits of aggressive and rapid proliferation rate and penetration along blood vessels. Therefore, MVI is one of the clinical features of liver cancer with a high risk of recurrence and a poor prognosis. There is a need to explore biomarkers and customized drugs for early diagnosis of MVI. Methods: Using gene expression of resected human HCC samples (Discovery cohort, n=240), we identified a transcriptomic signature predictive of MVI. Subsequently, we performed integrated analyses using data from the cancer dependency map (DepMap) project, including multi-omics based cancer-specific molecular characterization, compound-based drug sensitivity screening, and integrative in-silico prediction approaches to investigate determinants of MVI. The resulting MVI-predictive transcriptomic signature was validated across multiple independent cohorts (TCGA-LIHC, n=373; KOREA, n=188; TOKYO, n=183; MODENA, n=78; ZHONGSHAN, n=159). Results: The MVI 1,028 genes signature was identified in the discovery cohort, and its predictive performance was robustly validated in the independent validation cohort (AUC = 0.889, p < 0.01). Multi-omics analyses revealed aggressive tumor biology associated with the MVI signature and highlighted specific biomarkers. Conclusions: Integrative multi-omics profiling of resectable HCC with MVI reveals biomarkers for the diagnosis of MVI and therapeutic target. This target will increase the therapeutic effect and play a key role in the precision medicine. Citation Format: Jisun So, Incheon Kang, Woo Young Kwon, Sung Hwan Lee. Integrated multi-omics approaches in resectable hepatocellular carcinoma with microvascular invasion for revealing therapeutic target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4017.