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Open Access Highly Accessed Research article

Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder

Jian-Ye Liu12, Yong-Hong Li12, Huan-Xin Lin1, Yi-Ji Liao1, Shi-Juan Mai1, Zhou-Wei Liu12, Zhi-Ling Zhang12, Li-Juan Jiang12, Jia-Xing Zhang1, Hsiang-Fu Kung1, Yi-Xin Zeng1, Fang-Jian Zhou12* and Dan Xie13*

Author Affiliations

1 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, No 651, Dongfeng Road East, Guangzhou 510060, China

2 Department of Urology, Cancer Center, Sun Yat-Sen University, No 651, Dongfeng Road East, Guangzhou 510060, China

3 Department of Pathology, Cancer Center, Sun Yat-Sen University, No 651, Dongfeng Road East, Guangzhou 510060, China

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BMC Cancer 2013, 13:349  doi:10.1186/1471-2407-13-349

Published: 19 July 2013

Abstract

Background

Yes-associated protein 1 (YAP 1), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene in multiple tumors. However, the expression dynamics of YAP 1 in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance are unclear.

Methods

In this study, the methods of quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC) were utilized to investigate mRNA/ protein expression of YAP 1 in UCBs. Spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data.

Results

Up-regulated expression of YAP 1 mRNA and protein was observed in the majority of UCBs by qRT-PCR and Western blotting, when compared with their paired normal bladder tissues. By IHC, positive expression of YAP 1 was examined in 113/213 (53.1%) of UCBs and in 6/86 (7.0%) of normal bladder specimens tissues. Positive expression of YAP 1 was correlated with poorer differentiation, higher T classification and higher N classification (P < 0.05). In univariate survival analysis, a significant association between positive expression of YAP 1 and shortened patients’ survival was found (P < 0.001). In different subsets of UCB patients, YAP 1 expression was also a prognostic indicator in patients with grade 2 (P = 0.005) or grade 3 (P = 0.046) UCB, and in patients in pT1 (P = 0.013), pT2-4 (P = 0.002), pN- (P < 0.001) or pT2-4/pN- (P = 0.004) stage. Importantly, YAP 1 expression (P = 0.003) together with pT and pN status (P< 0.05) provided significant independent prognostic parameters in multivariate analysis.

Conclusions

Our findings provide evidences that positive expression of YAP 1 in UCB may be important in the acquisition of an aggressive phenotype, and it is an independent biomarker for poor prognosis of patients with UCB.

Keywords:
Urothelial carcinoma of the bladder; YAP 1; Immunohistochemistry; Prognosis