1. Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder
- Author
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Yi Xin Zeng, Yi Ji Liao, Fang Jian Zhou, Li Juan Jiang, Jia Xing Zhang, Jian Ye Liu, Shi Juan Mai, Zhi Ling Zhang, Yong Hong Li, Dan Xie, Hsiang-Fu Kung, Zhou Wei Liu, and Huan Xin Lin
- Subjects
Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,YAP 1 ,Blotting, Western ,Kaplan-Meier Estimate ,Real-Time Polymerase Chain Reaction ,Young Adult ,Surgical oncology ,Biomarkers, Tumor ,Genetics ,Carcinoma ,Humans ,Medicine ,Survival analysis ,Adaptor Proteins, Signal Transducing ,Aged ,Proportional Hazards Models ,Aged, 80 and over ,Carcinoma, Transitional Cell ,Hippo signaling pathway ,Oncogene ,Urothelial carcinoma of the bladder ,business.industry ,YAP-Signaling Proteins ,Middle Aged ,Prognosis ,Phosphoproteins ,medicine.disease ,Immunohistochemistry ,Up-Regulation ,Real-time polymerase chain reaction ,Urinary Bladder Neoplasms ,Oncology ,Cancer research ,Biomarker (medicine) ,Female ,business ,Research Article ,Transcription Factors - 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.
- Published
- 2013
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