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

Saranya Chidambaranathan Reghupaty, Sadia Kanwal, Rachel G. Mendoza, Eva Davis, Haiwen Li, Zhao Lai, Mikhail G. Dozmorov, Milton Omar Faison, Rafat Ali Siddiqui, Devanand Sarkar

Research output: Contribution to journalArticlepeer-review


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 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 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.

Original languageEnglish (US)
Article number4283
Issue number17
StatePublished - Sep 2023


  • ginger
  • hepatocellular carcinoma (HCC)
  • inflammation
  • interferon
  • interferon-stimulated genes (ISGs)
  • racial disparity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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