Detailed Abstract
[Plenary Session]
[PL 2] Consensus molecular subtypes reflecting distinct clinical phenotypes of hepatocellular carcinoma: Deciphering resectable hepatocellular carcinoma
Sung Hwan LEE*1, 2, Sun Young YIM3, Sang-Hee KANG4, Bo Hwa SOHN1, Yun Seong JEONG1, Ji-Hyun SHIN1, You Rhee CHOI1, Jae-Jun SHIM5, Jihoon KIM3, Henry LI6, Sheng GUO6, Randy JOHNSON7, Ahmed KASEB8, Koo Jeong KANG9, David WHEELER10, Ju-Seog LEE1
1Department of Systems Biology, University of Texas MD Anderson Cancer Center, USA
2Department of Surgery, CHA Bundang Medical Center, CHA University, Korea
3Department of Internal Medicine, Korea University College of Medicine, Korea
4Department of Surgery, Korea University College of Medicine, Korea
5Department of Internal Medicine, Kyung Hee University, Korea
6Global Scientific Research and Innovation Division, Crown Bioscience Inc., USA
7Department of Cancer Biology, University of Texas MD Anderson Cancer Center, USA
8Department of GI Medical Oncology, University of Texas MD Anderson Cancer Center, USA
9Department of Surgery, Keimyung University Dongsan Medical Center, Korea
10Department of Molecular and Human Genetics, Baylor College of Medicine, USA
Introduction : Hepatocellular carcinoma (HCC) is a heterogeneous disease with therapeutic resistance even in the early stage. Current genomic subtyping systems reflect the heterogeneity of HCC, but its clinical use is hampered by discrepancies among different studies.
Methods : By integrating 15 previously established genomic signatures for HCC subtypes, we identified five clinically and molecularly distinct consensus subtypes using transcriptomic data from 8 HCC cohorts with 1754 patients (Discovery set; n=1006, Validation set; n=748).
Results : We demonstrated five consensus subtypes of HCC showing distinct molecular and clinical features regarding STM, CIN, IMH, BCM, and DLP subtypes. Briefly, STM (STeM) is characterized by high stem cell features, vascular invasion, and sensitivity to sorafenib. CIN (Chromosome INstable) has moderate stem cell features, but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity predicting possible responders for immunotherapies. BCM (Beta-Catenin with Male high predominance) is characterized by prominent beta-catenin activation, low miRNA expression, and hypomethylation. DLP (Differentiated and Low Proliferation) is differentiated with high HNF4A activity. Lastly, we developed and validated a robust predictor of integrated consensus subtype with subtype-specific serum biomarkers using integrative genomic and statistical analysis.
Conclusions : Consensus subtypes of HCC from the comprehensive genomic analysis showed distinct biological and clinical phenotypes, including different dependency for oncogenic pathways and discriminated therapeutic efficacy. Based on the clinical relevance of consensus subtypes for current available therapeutic options in terms of molecular target therapies and immunotherapies, our findings may provide the foundation for rationalized biomarker-based clinical trials for resectable HCC.
Methods : By integrating 15 previously established genomic signatures for HCC subtypes, we identified five clinically and molecularly distinct consensus subtypes using transcriptomic data from 8 HCC cohorts with 1754 patients (Discovery set; n=1006, Validation set; n=748).
Results : We demonstrated five consensus subtypes of HCC showing distinct molecular and clinical features regarding STM, CIN, IMH, BCM, and DLP subtypes. Briefly, STM (STeM) is characterized by high stem cell features, vascular invasion, and sensitivity to sorafenib. CIN (Chromosome INstable) has moderate stem cell features, but high genomic instability and low immune activity. IMH (IMmune High) is characterized by high immune activity predicting possible responders for immunotherapies. BCM (Beta-Catenin with Male high predominance) is characterized by prominent beta-catenin activation, low miRNA expression, and hypomethylation. DLP (Differentiated and Low Proliferation) is differentiated with high HNF4A activity. Lastly, we developed and validated a robust predictor of integrated consensus subtype with subtype-specific serum biomarkers using integrative genomic and statistical analysis.
Conclusions : Consensus subtypes of HCC from the comprehensive genomic analysis showed distinct biological and clinical phenotypes, including different dependency for oncogenic pathways and discriminated therapeutic efficacy. Based on the clinical relevance of consensus subtypes for current available therapeutic options in terms of molecular target therapies and immunotherapies, our findings may provide the foundation for rationalized biomarker-based clinical trials for resectable HCC.
SESSION
Plenary Session
Room A 7/29/2020 11:15 AM - 11:30 AM