title: Elevated ZC3H15 increases HCC growth and predicts poor survival after surgical resection.
abstract: Zinc finger CCCH-type containing 15 (ZC3H15), also known as DRG family regulatory protein 1 (DFRP1), is a highly conserved eukaryotic protein that associates with active translation machinery. The aim of our study was to explore the clinical relevance and intrinsic functions of ZC3H15 in hepatocellular carcinoma (HCC). We constructed a cohort with 261 tumor and matched normal tissues from HCC patients. ZC3H15 protein and mRNA levels were determined using immunohistochemistry, western blot analysis, and quantitative polymerase chain reaction. ZC3H15 was highly expressed in the majority of HCC cases, and high ZC3H15 levels were significantly associated with high serum a-fetoprotein (AFP) levels (>20 ng/mL) and vascular invasion. Kaplan-Meier and Cox regression data indicated that elevated ZC3H15 was an independent predictor for HCC-specific disease-free survival (hazards ratio [HR], 1.789; 95% confidence interval [95% CI], 1.298-2.466 [P=0.0004]) and overall survival (HR, 1.613; 95% CI, 1.120-2.322 [P=0.0101]). Interaction of ZC3H15 with TRAF2 increased activation of NFκB signaling. These results suggest ZC3H15 is an independent prognostic marker in HCC patients that is clinicopathologically associated with tumor invasion and serum AFP levels.
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Bei-Ge
authors.initials: BG
authors.lastname: Jiang
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.
authors.forename: Zheng-Hua
authors.initials: ZH
authors.lastname: Wan
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Li
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Fu
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Shen-Xian
authors.initials: SX
authors.lastname: Yuan
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Ruo-Yu
authors.initials: RY
authors.lastname: Wang
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Gu
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Dong
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Ze-Ya
authors.initials: ZY
authors.lastname: Pan
authors.affiliation: Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhou
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D046888:Tissue Array Analysis; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D016328:NF-kappa B; C101338:PSMD2 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D047992:TNF Receptor-Associated Factor 2; C583533:ZC3H15 protein, human; D000509:alpha-Fetoproteins
keywords: NFκB; TRAF2; ZC3H15; hepatocellular carcinoma