Molecular Dysregulation Underlying Racial Disparity in Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma (HCC) is a highly fatal disease with mortality running parallel to its incidence. For HCC patients, there is a statistically significant increase in incidence and mortality and a decrease in 5-year survival rates in African American (AA)/Black patients compared to non-Hispanic (white) patients. There is a gap of knowledge in our understanding of the molecular mechanism underlying the HCC racial disparity between AA/Black and white patients. To address this issue, we analyzed existing RNA-sequencing (RNA-seq) data from HCC patients in the TCGA database, and performed RNA-seq in 14 white and 19 AA/Black HCC patients from Virginia Commonwealth University. In both analysis the only pathway which showed statistically significant activation in AA/Black patients, compared to white patients, was type I interferon (IFN-I) signaling. A four gene signature of IFN-I-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors compared to their white counterparts. HCC is a disease of chronic inflammation and IFN-I function as a pro-inflammatory and immunosuppressive cytokine. These findings suggest a potential role of IFN-I in conferring disparity in AA/Black HCC patients. We compared gene expression profiles of AA/Black and white HCC patients using TCGA and in-house-generated data.