Hepatic RIG-I Predicts Survival and Interferon-alpha Therapeutic Response in Hepatocellular Carcinoma
Menée sur des échantillons tumoraux prélevés sur 443 patients chinois atteints d'un carcinome hépatocellulaire, cette étude suggère que la mesure de l'expression du gène RIG-I est associée au pronostic de la maladie et à la réponse à un traitement par interféron alpha
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
"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
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Lower hepatic RIG-I expression in men may contribute to HCC gender disparity
Cancer cell , résumé, 2012