Research Papers:
Elevated ZC3H15 increases HCC growth and predicts poor survival after surgical resection
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Abstract
Bei-ge Jiang1,*, Zheng-hua Wan2,*, Jian Huang1,*, Li-mei Li3, Hui Liu1, Si-yuan Fu1, Yuan Yang1, Jin Zhang1, Shen-xian Yuan1, Ruo-yu Wang1, Yun Yang1, Fang-ming Gu1, Li-wei Dong2, Ze-ya Pan1, Wei-ping Zhou1
1Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China
2International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China
3State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, P. R. China
*These authors have contributed equally to this work
Correspondence to:
Wei-ping Zhou, email: [email protected]
Ze-ya Pan email: [email protected]
Keywords: hepatocellular carcinoma, ZC3H15, NFκB, TRAF2
Received: December 22, 2015 Accepted: April 24, 2016 Published: May 14, 2016
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.
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