Cancers: Dysregulation of Type I Interferon (IFN-I) Signaling: A Potential Contributor to Racial Disparity in Hepatocellular Carcinoma (HCC) (Lai)

Hepatocellular carcinoma (HCC) is the most common primary liver cancer arising from the liver cells, and hepatocytes. Chronic liver inflammation plays a key role in the development of HCC. HCC is a highly fatal disease where race/ethnicity plays a vital role in determining incidence, mortality, and survival rates. There is a knowledge gap in our understanding of the molecular mechanism underlying the HCC racial disparity between African-American (AA)/Black and White patients. Global gene expression analysis between AA/Black and White HCC patients identified the activation of a key inflammatory pathway in AA/Black tumors. Ginger extract (GE) is known for its anti-inflammatory properties. GE inhibited the proliferation of HCC cells, and our data suggest that HCC cell lines from AA/Black patients responded better to GE compared to those from White and Asian patients. These findings suggest that AA/Black HCC patients might benefit from a holistic dietary approach, which includes ginger.

African-American (AA)/Black hepatocellular carcinoma (HCC) patients have increased incidence and decreased survival rates compared to non-Hispanic (White) patients, the underlying molecular mechanism of which is not clear. Analysis of existing RNA-sequencing (RNA-seq) data in The Cancer Genome Atlas (TCGA) and in-house RNA-sequencing of 14 White and 18 AA/Black HCC patients revealed statistically significant activation of type I interferon (IFN-I) signaling pathway in AA/Black patients. A four-gene signature of IFN-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors versus White. HCC is a disease of chronic inflammation, and IFN-Is function as pro-inflammatory cytokines. We tested the efficacy of ginger extract (GE), a dietary compound known for anti-inflammatory properties, on HCC cell lines derived from White (HepG2), AA/Black (Hep3B and O/20), and Asian (HuH-7) patients. GE exhibited a significantly lower IC₅₀ on Hep3B and O/20 cells than on HepG2 and HuH-7 cells. The GE treatment inhibited the activation of downstream mediators of IFN-I signaling pathways and the expression of ISGs in all four HCC cells. Our data suggest that ginger can potentially attenuate IFN-I-mediated signaling pathways in HCC, and cells from AA/Black HCC patients may be more sensitive to ginger. AA/Black HCC patients might benefit from a holistic diet containing ginger.