Abstract 2272: Integration of multi-omics data reveals molecular features of Hispanic hepatocellular carcinoma

Abstract

Abstract Hepatocellular carcinoma (HCC) is the major type of liver cancer and one of the few cancers with a steady increase in incidence and mortality rate over the past several decades in the USA. It disproportionately affects Hispanics in the USA with an incidence and mortality rate about two to three times higher in Hispanics than in non-Hispanic whites. To identify molecular features associated with the Hispanic HCC we have generated genome-wide sequencing (i.e., exome-seq, RNA-seq) data and mass spectrometry-based proteomics data from HCC tumor and matched blood and/or adjacent normal tissues of Hispanic patients based in South Texas. The landscape of somatic mutation in HCC tumors revealed the aflatoxin-induced mutational signature (COSMIC) in some patients indicating an association of aflatoxin mediated toxicity in them. Similar to The Cancer Genome Atlas (TCGA) study, with predominant non-Hispanic HCC tumors, we could identify the most frequent somatic mutations in CTNNB1 and TP53. Other frequently (>10%) mutated genes in our patients appear to be mutated at relatively lower rate in the TCGA patients. Mutation(s) in some of the frequently mutated genes might contribute to the significant enrichment of cellular signaling pathways observed from the Gene Set Enrichment Analysis (GSEA) using paired RNA-seq data. Single sample GSEA (ssGSEA) of our RNA-seq and proteomic data sets revealed two clusters of HCC tumors, denoted as H1 and H2 clusters, with striking differences in various signaling pathways and cellular functions. Patients from the H1 cluster and two sub-clusters within the H2 cluster showed a significant difference in their survival rate based on overall survival information from the TCGA study. The transcriptomic data from Hispanic & non-Hispanic HCC identified activated immune evasion mechanisms in H1 patients. Sorafenib treatment was found to be associated with a lower hazard ratio for overall survival in patients from the H1 cluster compared to the H2 cluster. In sum, we have identified genes more frequently mutated in Hispanic HCC than in non-Hispanic HCC, and cellular and tissue functions significantly enriched only in the Hispanic HCC. We also report a novel classification of HCC tumors with significant differences in various cellular signaling pathways and overall survival. Our findings might be used as biomarkers for the early prediction and better therapeutic management of HCC. Citation Format: Debodipta Das, Xiaojing Wang, Yu-Chiao Chiu, Hakim Bouamar, Yidong Chen, Siyuan Zheng, Francisco G. Cigarroa, Lu-Zhe Sun. Integration of multi-omics data reveals molecular features of Hispanic hepatocellular carcinoma [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 2272.