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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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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 |
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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 |
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