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Cancer Cell. 2014 Jan 13;25(1):49-63. doi: 10.1016/j.ccr.2013.11.011. Epub 2013 Dec 19.

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

Author information

1
National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China; National Key Laboratory of Medical Molecular Biology and Department of Immunology, Chinese Academy of Medical Sciences, Beijing 100005, China.
2
National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
3
Department of Hepatic Surgery, Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai 200032, China.
4
Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
5
Departments of Pathology and Surgery, State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong 999077, China.
6
National Key Laboratory of Medical Molecular Biology and Department of Immunology, Chinese Academy of Medical Sciences, Beijing 100005, China.
7
Department of Organ Transplantation, Shanghai Changzheng Hospital, Shanghai 200003, China.
8
Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
9
Department of Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning 530021, China.
10
Department of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
11
Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
12
Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
13
National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China; National Key Laboratory of Medical Molecular Biology and Department of Immunology, Chinese Academy of Medical Sciences, Beijing 100005, China. Electronic address: caoxt@immunol.org.

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.

PMID:
24360797
DOI:
10.1016/j.ccr.2013.11.011
[Indexed for MEDLINE]
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