Abstract 768: Consensus subtypes of hepatocellular carcinoma associated with clinical outcomes

Abstract

Abstract Background & Aims: While many studies revealed transcriptomic subtypes of hepatocellular carcinoma (HCC), they are not translated to the clinic yet due to lack of consensus. We aim to examine consensus of transcriptomic subtypes and uncover their clinical significance. Methods: We integrated 15 previously established transcriptomic signatures for HCC to uncover consensus subtypes. We also developed and validated a robust predictor of consensus subtype with 100 genes (PICS100). Informatics and statistics approaches were applied to find clinical relevant association of genomic features. Patient derived xenograft (PDX) models were used for testing hypothesis from analysis of transcriptomic data. Results: We identified 5 clinically and molecularly distinct consensus subtypes. STM (STeM) is characterized by high stem cell features, vascular invasion, and poor prognosis. CIN (Chromosomal INstability) has moderate stem cell features but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity. BCM (Beta-Catenin with high Male predominance) is characterized by prominent β-catenin activation, low miRNA expression, hypomethylation, and high sensitivity to sorafenib. DLP (Differentiated and Low Proliferation) is differentiated with high HNF4A activity. We also identified potential serum biomarkers that can stratify patients into 5 subtypes. Conclusions: Five HCC subtypes are associated with potential response to treatments and highly conserved in pre-clinical models, providing a framework for selecting the most appropriate models for preclinical studies of new drugs and potentially for future clinical trials. Citation Format: Ju-Seog Lee, Sun Young Yim, Sung Hwan Lee, Yun Seong Jeong. Consensus subtypes of hepatocellular carcinoma associated with clinical outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 768.