Hispanics in the US experience a disproportionate burden of hepatocellular carcinoma (HCC) with an overall incidence and cancer-related mortality nearly two times higher than non-Hispanic whites. The genomic characteristics and underlying molecular mechanisms driving tumorigenesis associated with HCC in Hispanic patients remain unknown. Here, we used 31 paired tumor and adjacent non-tumor liver samples from Hispanic patients in South Texas to perform integrated genomic, transcriptomic, proteomic, and metabolomic analyses. Similar to HCC in other ethnic groups, CTNNB1 and TP53 were found to have the most frequent somatic mutations in the Hispanic HCC. On the other hand, AXIN2 and to a lesser degree MTOR appear more frequently mutated in the Hispanics compared to the various ethnic groups included in The Cancer Genome Atlas (TCGA) study. Somatic mutations in the Hispanic HCC showed signatures of tobacco chewing and aflatoxin exposure, which are different from the signatures found frequently in the liver cancer patients in the TCGA study. The WNT, TP53, & cell cycle were the most frequently altered oncogenic pathways in our cohort. Unsupervised clustering of patients, based on the enrichment scores from single sample Gene Set Enrichment Analysis (ssGSEA) using our tumor and nontumor paired RNA-Seq and proteomic data, revealed two clusters with striking differences in various signaling pathways and cellular functions. A similar clustering pattern with a significant difference in overall survival was seen in the patients from the TCGA study. Irrespective of ethnicity, immune infiltration in the tumor microenvironment and liver function-related pathways were significantly different between patients in these clusters. Integrated transcriptomic, proteomic, and metabolomic analyses identified significant negative enrichments in gluconeogenesis, TCA cycle, and glutamate metabolism in Hispanic HCC. These results suggest the existence of molecular mechanisms either unique in Hispanics or similar to non-Hispanic HCC, especially from the TCGA study. Our findings might provide insights to developing predictive biomarkers for the early diagnosis and novel therapeutics for the management of HCC.

Citation Format: Debodipta Das, Xiaojing Wang, Yu-Chiao Chiu, Hakim Bouamar, Yidong Chen, Siyuan Zheng, Francisco G. Cigarroa, Lu-Zhe Sun. Comprehensive multi-omic characterization of hepatocellular carcinoma in Hispanic patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3175.