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.
Copyright © 2014 Elsevier Inc. All rights reserved.
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
-
Receptors, Immunologic
-
Sex Characteristics
-
Signal Transduction / physiology
-
Tissue Array Analysis
-
Tumor Suppressor Proteins / metabolism
-
Young Adult
Substances
-
Antineoplastic Agents
-
Biomarkers, Tumor
-
Interferon-alpha
-
Receptors, Immunologic
-
Tumor Suppressor Proteins
-
RIGI protein, human
-
DEAD Box Protein 58
-
DEAD-box RNA Helicases