Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder.
Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder.
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YAP 1 过度表达导致人膀胱尿路上皮癌的进展特征和不良预后
DOI：
10.1186/1471-2407-13-349
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发表时间：
2013-07-19
期刊：
影响因子：
3.8
通讯作者：
Xie D
中科院分区：
文献类型：
--
作者：
Liu JY;Li YH;Lin HX;Liao YJ;Mai SJ;Liu ZW;Zhang ZL;Jiang LJ;Zhang JX;Kung HF;Zeng YX;Zhou FJ;Xie D
染料相关蛋白1 （YAP 1）是Hippo通路的核效应物，是器官大小的关键调节因子，也是多种肿瘤的候选人类癌基因。然而，YAP 1在膀胱尿路上皮癌（UCB）中的表达动态及其临床/预后意义尚不清楚。方法采用实时荧光定量聚合酶链反应（qRT-PCR）、免疫印迹（Western blotting）和免疫组化（IHC）方法检测YAP - 1在UCBs中的mRNA/蛋白表达。采用Spearman秩相关、Kaplan-Meier图和Cox比例风险回归模型对数据进行分析。结果通过qRT-PCR和Western blotting检测，与配对的正常膀胱组织相比，大多数ucb中YAP 1 mRNA和蛋白的表达均受sup调控。通过免疫组化检测，yap1阳性表达在113/213例（53.1%）ucb和6/86例（7.0%）正常膀胱标本组织中。YAP 1阳性表达与分化较差、T分型较高、N分型较高相关（P< 0.05）。在单因素生存分析中，YAP 1阳性表达与缩短患者生存期之间存在显著相关性（P< 0.001）。在不同亚群的UCB患者中，YAP 1表达也是2级（P= 0.005）或3级（P= 0.046） UCB患者以及pT1 （P= 0.013）、pT2-4 （P= 0.002）、pN- (P< 0.001)或pT2-4/pN- (P= 0.004)期患者的预后指标。重要的是，YAP 1表达（P= 0.003）与pT和pN状态（P< 0.05）在多因素分析中提供了重要的独立预后参数。结论YAP 1在UCB中阳性表达可能在侵袭性表型的获得中起重要作用，是UCB患者预后不良的独立生物标志物。
BackgroundYes-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.MethodsIn 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.ResultsUp-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.ConclusionsOur 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.
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影响因子：
64.5
作者：
Zender, Lars;Spector, Mona S.;Lowe, Scott W.
通讯作者：
Lowe, Scott W.
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影响因子：
5.7
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
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影响因子：
6.2
作者：
Xu, Michelle Z.;Yao, Tzy-Jyun;Lee, Nikki P. Y.;Ng, Irene O. L.;Chan, Yuk-Tat;Zender, Lars;Lowe, Scott W.;Poon, Ronnie T. P.;Luk, John M.
通讯作者：
Luk, John M.
影响因子：
64.5
作者：
Harvey, KF;Pfleger, CM;Hariharan, IK
通讯作者：
Hariharan, IK