title: 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.affiliation: 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.
authors.forename: Jin
authors.initials: J
authors.lastname: Hou
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Hepatic Surgery, Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai 200032, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.affiliation: Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Departments of Pathology and Surgery, State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong 999077, China.
authors.forename: Irene O L
authors.initials: IO
authors.lastname: Ng
authors.affiliation: Department of Hepatic Surgery, Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai 200032, China.
authors.forename: Huichuan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Hepatic Surgery, Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai 200032, China.
authors.forename: Lunxiu
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Hepatic Surgery, Liver Cancer Institute and Zhongshan Hospital, Institutes of Biomedical Science, Fudan University, Shanghai 200032, China.
authors.forename: Shuangjian
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Departments of Pathology and Surgery, State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong 999077, China.
authors.forename: Joyce M F
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Departments of Pathology and Surgery, State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong 999077, China.
authors.forename: Chung-Mau
authors.initials: CM
authors.lastname: Lo
authors.affiliation: Departments of Pathology and Surgery, State Key Laboratory for Liver Research, University of Hong Kong, Hong Kong 999077, China.
authors.forename: Kwan
authors.initials: K
authors.lastname: Man
authors.affiliation: Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: National Key Laboratory of Medical Molecular Biology and Department of Immunology, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Yingyun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhu
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Organ Transplantation, Shanghai Changzheng Hospital, Shanghai 200003, China.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Organ Transplantation, Shanghai Changzheng Hospital, Shanghai 200003, China.
authors.forename: Guoshan
authors.initials: G
authors.lastname: Ding
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Shi-Mei
authors.initials: SM
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Surgery, Affiliated Tumor Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: Anmin
authors.initials: A
authors.lastname: Liang
authors.affiliation: Department of Medical Genetics, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Transplantation and Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Tingbo
authors.initials: T
authors.lastname: Liang
authors.affiliation: National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011971:Receptors, Immunologic; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016898:Interferon-alpha; D011971:Receptors, Immunologic; D025521:Tumor Suppressor Proteins; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases