PRAF2 expression indicates unfavorable clinical outcome in hepatocellular carcinoma.
PRAF2 expression indicates unfavorable clinical outcome in hepatocellular carcinoma.
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PRAF2表达表明肝细胞癌的不良临床结果
DOI：
10.2147/cmar.s166789
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发表时间：
2018
影响因子：
3.3
通讯作者：
Yun JP
中科院分区：
文献类型：
--
作者：
Wang CH;Liu LL;Liao DZ;Zhang MF;Fu J;Lu SX;Chen SL;Wang H;Cai SH;Zhang CZ;Zhang HZ;Yun JP
前言：Prenylated RAB受体1结构域家族成员2(PRAF2)是一种新的癌基因，在多种人类肿瘤的发生发展中起重要作用，但其在肝细胞癌中的作用尚不清楚。材料与方法分别用定量逆转录聚合酶链式反应和免疫印迹法检测新鲜肝组织和518例石蜡包埋肝细胞癌组织中PRAF2mRNA和蛋白的表达。通过学生t检验、Kaplan-Meier检验和多因素Cox回归分析，确定PRAF2表达与临床预后的相关性。通过体外和体内裸鼠模型的细胞存活率、集落形成和迁移实验研究了PRAF2在肝癌中的作用。结果肝细胞癌组织中PRAF2的表达在mRNA和蛋白水平均显著高于非肿瘤组织。Kaplan-Meier分析表明，在518名肝癌患者的队列中，PRAF2的高表达与较差的总体生存相关。分层生存分析证实了PRAF2的预后意义。多变量COX回归模型显示PRAF2是影响肝细胞癌总生存率的独立不良预后因素(风险比=1.244，95%CI：1.039-1.498，P<；0.017)。体外实验表明，PRAF2过表达可显著提高细胞存活率、集落形成和细胞迁移能力。此外，异位表达PRAF2促进了体内肿瘤的生长和转移。结论PRAF2在肝细胞癌中升高，是一种新的预测肝细胞癌患者预后的不良生物标志物。
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.