title: Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder.
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.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, No 651, Dongfeng Road East, Guangzhou 510060, China.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Liu
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Huan-Xin
authors.initials: HX
authors.lastname: Lin
authors.forename: Yi-Ji
authors.initials: YJ
authors.lastname: Liao
authors.forename: Shi-Juan
authors.initials: SJ
authors.lastname: Mai
authors.forename: Zhou-Wei
authors.initials: ZW
authors.lastname: Liu
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhang
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Jiang
authors.forename: Jia-Xing
authors.initials: JX
authors.lastname: Zhang
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Fang-Jian
authors.initials: FJ
authors.lastname: Zhou
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000091102:YAP-Signaling Proteins; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human