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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Jian-Ye, Li, Yong-Hong, Lin, Huan-Xin, Liao, Yi-Ji, Mai, Shi-Juan, Liu, Zhou-Wei, Zhang, Zhi-Ling, Jiang, Li-Juan, Zhang, Jia-Xing, Kung, Hsiang-Fu, Zeng, Yi-Xin, Zhou, Fang-Jian, Xie, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750259/
https://www.ncbi.nlm.nih.gov/pubmed/23870412
http://dx.doi.org/10.1186/1471-2407-13-349
_version_ 1782477088957136896
author Liu, Jian-Ye
Li, Yong-Hong
Lin, Huan-Xin
Liao, Yi-Ji
Mai, Shi-Juan
Liu, Zhou-Wei
Zhang, Zhi-Ling
Jiang, Li-Juan
Zhang, Jia-Xing
Kung, Hsiang-Fu
Zeng, Yi-Xin
Zhou, Fang-Jian
Xie, Dan
author_facet Liu, Jian-Ye
Li, Yong-Hong
Lin, Huan-Xin
Liao, Yi-Ji
Mai, Shi-Juan
Liu, Zhou-Wei
Zhang, Zhi-Ling
Jiang, Li-Juan
Zhang, Jia-Xing
Kung, Hsiang-Fu
Zeng, Yi-Xin
Zhou, Fang-Jian
Xie, Dan
author_sort Liu, Jian-Ye
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3750259
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-37502592013-08-24 Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder Liu, Jian-Ye Li, Yong-Hong Lin, Huan-Xin Liao, Yi-Ji Mai, Shi-Juan Liu, Zhou-Wei Zhang, Zhi-Ling Jiang, Li-Juan Zhang, Jia-Xing Kung, Hsiang-Fu Zeng, Yi-Xin Zhou, Fang-Jian Xie, Dan BMC Cancer Research Article 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. BioMed Central 2013-07-19 /pmc/articles/PMC3750259/ /pubmed/23870412 http://dx.doi.org/10.1186/1471-2407-13-349 Text en Copyright © 2013 Liu et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Jian-Ye
Li, Yong-Hong
Lin, Huan-Xin
Liao, Yi-Ji
Mai, Shi-Juan
Liu, Zhou-Wei
Zhang, Zhi-Ling
Jiang, Li-Juan
Zhang, Jia-Xing
Kung, Hsiang-Fu
Zeng, Yi-Xin
Zhou, Fang-Jian
Xie, Dan
Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder
title Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder
title_full Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder
title_fullStr Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder
title_full_unstemmed Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder
title_short Overexpression of YAP 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder
title_sort overexpression of yap 1 contributes to progressive features and poor prognosis of human urothelial carcinoma of the bladder
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750259/
https://www.ncbi.nlm.nih.gov/pubmed/23870412
http://dx.doi.org/10.1186/1471-2407-13-349
work_keys_str_mv AT liujianye overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT liyonghong overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT linhuanxin overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT liaoyiji overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT maishijuan overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT liuzhouwei overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT zhangzhiling overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT jianglijuan overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT zhangjiaxing overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT kunghsiangfu overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT zengyixin overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT zhoufangjian overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder
AT xiedan overexpressionofyap1contributestoprogressivefeaturesandpoorprognosisofhumanurothelialcarcinomaofthebladder