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

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.

• Authors: Jin Hou, Ye Zhou, Yuanyuan Zheng, Jia Fan, Weiping Zhou, Irene O L Ng, Huichuan Sun, Lunxiu Qin, Shuangjian Qiu, Joyce M F Lee, Chung-Mau Lo, Kwan Man, Yuan Yang, Yun Yang, Yingyun Yang, Qian Zhang, Xuhui Zhu, Nan Li, Zhengxin Wang, Guoshan Ding, Shi-Mei Zhuang, Limin Zheng, Xiaoling Luo, Yuan Xie, Anmin Liang, Zhugang Wang, Ming Zhang, Qiang Xia, Tingbo Liang, Yizhi Yu, Xuetao Cao
• Journal: Cancer cell (Cancer Cell) Vol. 25 Issue 1 Pg. 49-63 (Jan 13 2014) ISSN: 1878-3686 [Electronic] United States
• PMID: 24360797 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Adult
• Aged
• Animals
• Antineoplastic Agents (therapeutic use)
• Biomarkers, Tumor (analysis)
• Carcinoma, Hepatocellular (drug therapy, metabolism, 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, metabolism, 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