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

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 - BMC Cancer (2013)

Bottom Line: In univariate survival analysis, a significant association between positive expression of YAP 1 and shortened patients' survival was found (P < 0.001).Importantly, YAP 1 expression (P = 0.003) together with pT and pN status (P< 0.05) provided significant independent prognostic parameters in multivariate analysis.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, No 651, Dongfeng Road East, Guangzhou 510060, China.

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.

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The expression of YAP 1 in UCB and normal bladder tissues. (A) Up-regulated expression of YAP 1 mRNA was examined by qRT-PCR in 12/14 UCB cases, when compared with paired normal bladder tissues. Expression levels were normalized for β-actin. Error bars, SD calculated from three parallel experiments. (B) Up-regulated expression of YAP 1 protein was detected by Western blotting in 11/14 UCB cases, when compared with paired normal bladder tissues. Expression levels were normalized with GAPDH. (C-F) The expression of YAP 1 in UCB and normal bladder tissues by IHC (100×). An UCB (case 39) tissue showed high expression of YAP 1, in which more than 90% of tumor cells were positively stained by YAP 1 in the nucleus (C), while its paired normal bladder urothelial mucosal tissue was negatively stained by YAP 1 (D). High expression of YAP 1 was observed in another UCB tissue (case 102), in which about 70% of tumor cells demonstrated a nuclear staining with a lesser cytoplasmic staining of YAP 1 (E). An UCB (case 78) was examined low expression of YAP 1, in which less than 5% of tumor cells showed nuclear staining of YAP 1 (F). An UCB (case 114) tissue showed high expression of YAP 1, in which more than 90% of tumor cells were positively stained by YAP 1 in the cytoplasm (G).
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Figure 1: The expression of YAP 1 in UCB and normal bladder tissues. (A) Up-regulated expression of YAP 1 mRNA was examined by qRT-PCR in 12/14 UCB cases, when compared with paired normal bladder tissues. Expression levels were normalized for β-actin. Error bars, SD calculated from three parallel experiments. (B) Up-regulated expression of YAP 1 protein was detected by Western blotting in 11/14 UCB cases, when compared with paired normal bladder tissues. Expression levels were normalized with GAPDH. (C-F) The expression of YAP 1 in UCB and normal bladder tissues by IHC (100×). An UCB (case 39) tissue showed high expression of YAP 1, in which more than 90% of tumor cells were positively stained by YAP 1 in the nucleus (C), while its paired normal bladder urothelial mucosal tissue was negatively stained by YAP 1 (D). High expression of YAP 1 was observed in another UCB tissue (case 102), in which about 70% of tumor cells demonstrated a nuclear staining with a lesser cytoplasmic staining of YAP 1 (E). An UCB (case 78) was examined low expression of YAP 1, in which less than 5% of tumor cells showed nuclear staining of YAP 1 (F). An UCB (case 114) tissue showed high expression of YAP 1, in which more than 90% of tumor cells were positively stained by YAP 1 in the cytoplasm (G).

Mentions: Our qRT-PCR results showed that YAP1 mRNA expression was upregulated in 12 of the 14 UCB samples compared with the paired normal bladder tissues (Figure 1A). Western blotting analyses also demonstrated upregulation of the YAP 1 protein in 11 of the 14 UCB samples compared to their normal counterparts (Figure 1B).


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

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 - BMC Cancer (2013)

The expression of YAP 1 in UCB and normal bladder tissues. (A) Up-regulated expression of YAP 1 mRNA was examined by qRT-PCR in 12/14 UCB cases, when compared with paired normal bladder tissues. Expression levels were normalized for β-actin. Error bars, SD calculated from three parallel experiments. (B) Up-regulated expression of YAP 1 protein was detected by Western blotting in 11/14 UCB cases, when compared with paired normal bladder tissues. Expression levels were normalized with GAPDH. (C-F) The expression of YAP 1 in UCB and normal bladder tissues by IHC (100×). An UCB (case 39) tissue showed high expression of YAP 1, in which more than 90% of tumor cells were positively stained by YAP 1 in the nucleus (C), while its paired normal bladder urothelial mucosal tissue was negatively stained by YAP 1 (D). High expression of YAP 1 was observed in another UCB tissue (case 102), in which about 70% of tumor cells demonstrated a nuclear staining with a lesser cytoplasmic staining of YAP 1 (E). An UCB (case 78) was examined low expression of YAP 1, in which less than 5% of tumor cells showed nuclear staining of YAP 1 (F). An UCB (case 114) tissue showed high expression of YAP 1, in which more than 90% of tumor cells were positively stained by YAP 1 in the cytoplasm (G).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750259&req=5

Figure 1: The expression of YAP 1 in UCB and normal bladder tissues. (A) Up-regulated expression of YAP 1 mRNA was examined by qRT-PCR in 12/14 UCB cases, when compared with paired normal bladder tissues. Expression levels were normalized for β-actin. Error bars, SD calculated from three parallel experiments. (B) Up-regulated expression of YAP 1 protein was detected by Western blotting in 11/14 UCB cases, when compared with paired normal bladder tissues. Expression levels were normalized with GAPDH. (C-F) The expression of YAP 1 in UCB and normal bladder tissues by IHC (100×). An UCB (case 39) tissue showed high expression of YAP 1, in which more than 90% of tumor cells were positively stained by YAP 1 in the nucleus (C), while its paired normal bladder urothelial mucosal tissue was negatively stained by YAP 1 (D). High expression of YAP 1 was observed in another UCB tissue (case 102), in which about 70% of tumor cells demonstrated a nuclear staining with a lesser cytoplasmic staining of YAP 1 (E). An UCB (case 78) was examined low expression of YAP 1, in which less than 5% of tumor cells showed nuclear staining of YAP 1 (F). An UCB (case 114) tissue showed high expression of YAP 1, in which more than 90% of tumor cells were positively stained by YAP 1 in the cytoplasm (G).
Mentions: Our qRT-PCR results showed that YAP1 mRNA expression was upregulated in 12 of the 14 UCB samples compared with the paired normal bladder tissues (Figure 1A). Western blotting analyses also demonstrated upregulation of the YAP 1 protein in 11 of the 14 UCB samples compared to their normal counterparts (Figure 1B).

Bottom Line: In univariate survival analysis, a significant association between positive expression of YAP 1 and shortened patients' survival was found (P < 0.001).Importantly, YAP 1 expression (P = 0.003) together with pT and pN status (P< 0.05) provided significant independent prognostic parameters in multivariate analysis.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, No 651, Dongfeng Road East, Guangzhou 510060, China.

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.

Show MeSH
Related in: MedlinePlus