J Cancer 2017; 8(19):4018-4026. doi:10.7150/jca.21226

Research Paper

Overexpression of CKAP4 is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma and Functions via Cyclin B Signaling

Chen-min Sun, Jiang Geng, Yang Yan, Xudong Yao, Min Liu

Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.

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Sun Cm, Geng J, Yan Y, Yao X, Liu M. Overexpression of CKAP4 is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma and Functions via Cyclin B Signaling. J Cancer 2017; 8(19):4018-4026. doi:10.7150/jca.21226. Available from http://www.jcancer.org/v08p4018.htm

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Aim: We aimed to study the role of CKAP4 in clear cell renal cell carcinoma (ccRCC), which is not reported previously.

Method: In silico exploration and validation using immunohistochemistry in ccRCC samples were used to identify the impact of CKAP4 expression on clinicopathological parameters. In vitro and in vivo studies were carried out to recapitulate the role of CKAP4 in ccRCC cell lines and animal models.

Results: Overexpression of CKAP4 occurred in 5% of ccRCC patients, who had significantly worsened prognosis. Increased CKAP4 expression was significantly associated with TNM staging and Fuhrman grade. Pathway analysis for genes coexpressed with CKAP4 in ccRCC unanimously revealed significant cell cycle progression at G2/M phase. Expressions of CCNB1 and CCNB2 were correlated with CKAP4 expression. Genetic upregulation of CKAP4 significantly increased proliferation, cell invasion and migration in ccRCC cell lines, and vice versa for CKAP4 silencing. CKAP4 silencing also significantly increased cell population at G2/M phase, while not influencing cell apoptosis. Silencing or upregulation of CKAP4 resulted in decreased or increased CCNB1/2 expressions, respectively. CCNB1/CDK1 inhibitor significantly inhibited colony formation ability and in vivo tumor growth of RCC cells with CKAP4 overexpression.

Conclusion: Upregulation of CKAP4 was associated with worsened characteristics of ccRCC. CKAP4 was related with CCNB signaling in ccRCC, which supported a role for CCNB/CDK inhibitor for ccRCC with such genotype.

Keywords: CKAP4, Renal cell carcinoma, VEGF, Prognosis