Cancer Cell
Volume 25, Issue 1, 13 January 2014, Pages 49-63
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Article
Hepatic RIG-I Predicts Survival and Interferon-α Therapeutic Response in Hepatocellular Carcinoma

https://doi.org/10.1016/j.ccr.2013.11.011Get rights and content
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Highlights

  • RIG-I is the most significantly downregulated IFN-stimulated gene in HCC

  • Patients with low RIG-I have shorter survival and poorer response to IFN-α therapy

  • RIG-I amplifies IFN-JAK-STAT effector signaling by enhancing STAT1 activation

  • Lower hepatic RIG-I expression in men may contribute to HCC gender disparity

Summary

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.

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These authors contributed equally to this work