Elevated ZC3H15 increases HCC growth and predicts poor survival after surgical resection

// Bei-ge Jiang 1, * , Zheng-hua Wan 2, * , Jian Huang 1, * , Li-mei Li 3 , Hui Liu 1 , Si-yuan Fu 1 , Yuan Yang 1 , Jin Zhang 1 , Shen-xian Yuan 1 , Ruo-yu Wang 1 , Yun Yang 1 , Fang-ming Gu 1 , Li-wei Dong 2 , Ze-ya Pan 1 , Wei-ping Zhou 1 1 Hepatic Surgery Department III, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, National Innovation Alliance for Hepatitis & Liver Cancer, Shanghai, P. R. China 2 International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, The Second Military Medical University, Shanghai, P. R. China 3 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 * These authors have contributed equally to this work Correspondence to: Wei-ping Zhou, email: ehbhwp@yeah.net Ze-ya Pan email: 378834858@qq.com 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.