Protein Expression of ZEB2 in Renal Cell Carcinoma and Its Prognostic Significance in Patient SurvivalReportar como inadecuado




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Background

ZEB2 has been reportedly shown to mediate the epithelial-to-mesenchymal transition EMT and disease aggressiveness in human tumors. However, the expression status of ZEB2 in renal cell carcinoma RCC and ZEB2’s clinicopathologic-prognostic significance are poorly understood.

Methodology-Principal Findings

In this study, tissue microarray, immunohistochemistry IHC and western blot analyses were utilized to investigate the ZEB2 expression status in RCC and adjacent renal tissue samples. In our study, samples from 116 RCC patients treated with radical nephrectomy were used as a training set to generate a ZEB2 optimal cut-point for patient outcome by receiver operating characteristic ROC analysis. For validation, the correlation of ZEB2 expression with the clinical characteristics and patient outcomes in another set including 113 patients was analyzed to validate the obtained cut-point. In the training and validation sets, high expression of ZEB2, defined by ROC analysis, predicted a poorer overall survival and progression-free survival, as evidenced by the univariate and multivariate analyses. In different subsets of overall patients, ZEB2 expression was also a prognostic indicator in patients with stage I-II, stage III-IV, grade 1-2 and grade 3-4 disease P<0.05. Downregulation of ZEB2 by shRNA decreased the migration and invasion ability of 769-P cells in vitro. Furthermore, high ZEB2 expression was positively correlated with vimentin expression and inversely linked to E-cadherin expression in RCC.

Conclusions-Significance

Our findings provide a basis for the concept that high ZEB2 expression in RCC may be important in the acquisition of an aggressive phenotype. This evidence suggests that ZEB2 overexpression examined by IHC is an independent biomarker for the poor prognosis of patients with RCC.



Autor: Yong Fang , Jinhuan Wei , Jiazheng Cao, Hongwei Zhao, Bing Liao, Shaopeng Qiu, Daohu Wang, Junhang Luo , Wei Chen

Fuente: http://plos.srce.hr/



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