Hepatic RIG-I Predicts Survival and Interferon-α Therapeutic Response in Hepatocellular Carcinoma

• Published in: Cancer cell 2014-01, Vol.25 (1), p.49-63
• Main Authors: Hou, Jin, Zhou, Ye, Zheng, Yuanyuan, Fan, Jia, Zhou, Weiping, Ng, Irene O.L., Sun, Huichuan, Qin, Lunxiu, Qiu, Shuangjian, Lee, Joyce M.F., Lo, Chung-Mau, Man, Kwan, Yang, Yuan, Yang, Yun, Yang, Yingyun, Zhang, Qian, Zhu, Xuhui, Li, Nan, Wang, Zhengxin, Ding, Guoshan, Zhuang, Shi-Mei, Zheng, Limin, Luo, Xiaoling, Xie, Yuan, Liang, Anmin, Wang, Zhugang, Zhang, Ming, Xia, Qiang, Liang, Tingbo, Yu, Yizhi, Cao, Xuetao
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccr.2013.11.011

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. [Display omitted] •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