Integrative multi-omics characterization of hepatocellular carcinoma in Hispanic patients

Abstract

Background: The incidence and mortality rates of hepatocellular carcinoma among Hispanic individuals in the United States are much higher than in non-Hispanic White people. We conducted multi-omics analyses to elucidate molecular alterations in hepatocellular carcinoma among Hispanic patients.

Methods: Paired tumor and adjacent nontumor samples were collected from 31 Hispanic hepatocellular carcinomas in South Texas for genomic, transcriptomic, proteomic, and metabolomic profiling. Serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed hepatocellular carcinoma.

Results: Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in South Texas Hispanic hepatocellular carcinoma patients, suggesting a predominant activation of the Wnt/β-catenin pathway. TERT promoter mutations were also statistically significantly more frequent in the Hispanic cohort (Fisher exact test, P < .05). Cell cycles and liver function were positively and negatively enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in serum samples of hepatocellular carcinoma patients (paired t test, P < .0001). Two hepatocellular carcinoma subtypes from our Hispanic cohort were identified and validated with the Cancer Genome Atlas liver cancer cohort. Patients with better overall survival showed higher activity of immune and angiogenesis signatures and lower activity of liver function-related gene signatures. They also had higher levels of immune checkpoint and immune exhaustion markers.

Conclusions: Our study revealed specific molecular features of Hispanic hepatocellular carcinoma and potential biomarkers for therapeutic management. It provides a unique resource for studying Hispanic hepatocellular carcinoma.