Cancer Management and Research (Jul 2018)
PRAF2 expression indicates unfavorable clinical outcome in hepatocellular carcinoma
Abstract
Chun-Hua Wang,1,2,* Li-Li Liu,1,2,* Ding-Zhun Liao,3,* Mei-Fang Zhang,1,2 Jia Fu,1,2 Shi-Xun Lu,1,2 Shi-Lu Chen,1,2 Hong Wang,1,2 Shao-Hang Cai,1,2 Chris Zhiyi Zhang,1,2 Hui-Zhong Zhang,2 Jing-Ping Yun1,2 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; 2Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; 3Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China *These authors contributed equally to this work Introduction: Prenylated Rab acceptor 1 domain family member 2 (PRAF2), a novel oncogene, has been shown to be essential for the development of several human cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear. Materials and methods: PRAF2 mRNA and protein expressions were examined in fresh tissues by quantitative reverse transcription-polymerase chain reaction and Western blot, respectively, and in 518 paraffin-embedded HCC samples by immunohistochemistry. The correlation of PRAF2 expression and clinical outcomes was determined by the Student’s t-test, Kaplan–Meier test, and multivariate Cox regression analysis. The role of PRAF2 in HCC was investigated by cell viability, colony formation, and migration assays in vitro and with a nude mouse model in vivo. Results: In our study, the PRAF2 expression was noticeably increased in HCC tissues at both the mRNA and protein levels compared with that of the nontumorous tissues. Kaplan–Meier analysis indicated that high PRAF2 expression was correlated with worse overall survival in a cohort of 518 patients with HCC. The prognostic implication of PRAF2 was verified by stratified survival analysis. The multivariate Cox regression model revealed PRAF2 as an independent poor prognostic factor for overall survival (hazard ratio = 1.244, 95% CI: 1.039–1.498, P<0.017) in HCC. The in vitro data demonstrated that PRAF2 overexpression markedly enhanced cell viability, colony formation, and cell migration. Moreover, ectopic expression of PRAF2 promoted tumor growth and metastasis in vivo. Conclusion: Collectively, we conclude that PRAF2 is increased in HCC and is a novel unfavorable biomarker for prognostic prediction for patients with HCC. Keywords: PRAF2, prognosis, proliferation, migration, hepatocellular carcinoma
