Hepatic RIG-I predicts survival and interferon-α therapeutic response in hepatocellular carcinoma

Cancer Cell. 2014 Jan 13;25(1):49-63. doi: 10.1016/j.ccr.2013.11.011. Epub 2013 Dec 19.

Abstract

In hepatocellular carcinoma (HCC), biomarkers for prediction of prognosis and response to immunotherapy such as interferon-α (IFN-α) would be very useful in the clinic. We found that expression of retinoic acid-inducible gene-I (RIG-I), an IFN-stimulated gene, was significantly downregulated in human HCC tissues. Patients with low RIG-I expression had shorter survival and poorer response to IFN-α therapy, suggesting that RIG-I is a useful prognosis and IFN-α response predictor for HCC patients. Mechanistically, RIG-I enhances IFN-α response by amplifying IFN-α effector signaling via strengthening STAT1 activation. Furthermore, we found that RIG-I deficiency promotes HCC carcinogenesis and that hepatic RIG-I expression is lower in men than in women. RIG-I may therefore be a tumor suppressor in HCC and contribute to HCC gender disparity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / metabolism*
  • Drug Resistance, Neoplasm / physiology
  • Female
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Interferon-alpha / therapeutic use*
  • Kaplan-Meier Estimate
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Sex Characteristics
  • Signal Transduction / physiology
  • Tissue Array Analysis
  • Tumor Suppressor Proteins / metabolism
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Interferon-alpha
  • Tumor Suppressor Proteins
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases

Associated data

  • GEO/GSE34674