Unraveling the molecular mechanism of racial disparity in hepatocellular carcinoma (HCC): A link between type I interferon (IFN-I) signaling and HCC disparity

Among HCC patients, there is a statistically significant increase in incidence and mortality as well as a decrease in 5-year survival rates in African-American (hereafter referred to as black) patients compared to non-Hispanic white (hereafter referred to as white) patients. Currently, there is a gap in our understanding of the molecular mechanism underlying this racial disparity. The purpose of this study is to unravel this molecular mechanism. Gene expression profiles were analyzed by RNA-sequencing (RNA-Seq). Canonical pathway analysis of the differentially expressed genes was performed by Ingenuity Pathway Analysis (IPA). Differential expression of the genes was validated by qRT-PCR and immunohistochemistry. The role of the identified genes in regulating proliferation was determined by transient knockdown by siRNA in a patient-derived xenograft (PDX) cell line established from a black HCC patient followed by MTT assay. In TCGA database, RNA-Seq data from 377 HCC patients were available, of which 17 were black and 184 were white. 279 genes were identified, with a p-value Persistent activation of the IFN-I signaling pathway might be a key determinant of racial disparity in black HCC patients. This pathway might be exploited to develop targeted treatment that work best for black HCC patients. Citation Format: Saranya Chidambaranathan-Reghupaty, Mikhail Dozmorov, Rachel Mendoza, Zhao Lai, Paul B. Fisher, Trevor Reichman, Devanand Sarkar. Unraveling the molecular mechanism of racial disparity in hepatocellular carcinoma (HCC): A link between type I interferon (IFN-I) signaling and HCC disparity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4001.