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野生型p53诱导磷酸酶1是膀胱移行细胞癌的一个预后标志物和治疗靶点。

Wild-type p53-induced phosphatase 1 is a prognostic marker and therapeutic target in bladder transitional cell carcinoma.

作者信息

Wang Zhi-Peng, Chen Shu-Yuan, Tian Ye

机构信息

Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.

Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.

出版信息

Oncol Lett. 2017 Feb;13(2):875-880. doi: 10.3892/ol.2016.5475. Epub 2016 Dec 8.

Abstract

Wild-type p53-induced phosphatase (Wip1) is an established oncogene and is associated with development of multiple forms of human cancer. However, the expression and role of Wip1 in human bladder transitional cell carcinoma (TCC) remains to be elucidated. In the present study, immunohistochemistry demonstrated that Wip1 was overexpressed in bladder TCC tissues compared with corresponding normal bladder tissues in 106 bladder TCC cases (P<0.0001). Furthermore, high expression levels of Wip1 were significantly associated with increasing tumor size (P=0.002), pathological grade (P=0.025), clinical T stage (P=0.001) and lymph nodal metastasis (P=0.003). Kaplan-Meier survival analysis identified that patients with high Wip1 expression levels exhibited a lower overall survival time (P<0.0001), and Cox proportional hazards regression model analysis demonstrated that Wip1 expression was an independent prognostic factor in patients with bladder TCC (P=0.025). In addition, downregulation of Wip1 expression by transfection with small interfering RNA in bladder cancer cells inhibited cell proliferation, invasion and migration (P<0.05), along with the upregulation of p53 protein levels (P<0.05). These findings suggest that Wip1 may function as a potential prognostic marker and therapeutic target in bladder cancer.

摘要

野生型p53诱导磷酸酶(Wip1)是一种已确定的癌基因,与多种人类癌症的发生发展相关。然而,Wip1在人膀胱移行细胞癌(TCC)中的表达及作用仍有待阐明。在本研究中,免疫组织化学显示,在106例膀胱TCC病例中,与相应的正常膀胱组织相比,Wip1在膀胱TCC组织中高表达(P<0.0001)。此外,Wip1的高表达水平与肿瘤大小增加(P=0.002)、病理分级(P=0.025)、临床T分期(P=0.001)及淋巴结转移(P=0.003)显著相关。Kaplan-Meier生存分析确定,Wip1表达水平高的患者总生存时间较短(P<0.0001),Cox比例风险回归模型分析表明,Wip1表达是膀胱TCC患者的独立预后因素(P=0.025)。此外,通过小干扰RNA转染下调膀胱癌细胞中Wip1的表达可抑制细胞增殖、侵袭和迁移(P<0.05),同时p53蛋白水平上调(P<0.05)。这些发现提示,Wip1可能作为膀胱癌潜在的预后标志物和治疗靶点发挥作用。

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