EZH2 Promotes Tumor Cell Progression Via Epigenetic Repression Of E-Cadherin And Prognosticates Patients Survival In Renal Cell Carcinoma

Prognostic value of EZH2 expression and activity in renal cell carcinoma:a prospective study Objective:It was demonstrated that increased expression of EZH2 correlated with aggressive clinical behavior in various malignancies. In this study, we aim to investigate the clinical and prognostic values of EZH2 expression in patients with renal cell carcinoma after surgery.Methods:We analyzed EZH2 expression and its activity as indicated by H3K27me3 levels comprising 373 patients with renal cell carcinoma in our institute. Outcome was assessed as overall survival and disease free survival using Kaplan-Meier analysis. Prognostic values of EZH2 and H3K27me3 expression for clinical outcomes were evaluated by Cox regression analysis. We used receiver operating characteristic to calculate diagnostic accuracy.Results:High EZH2 expression correlates with poor overall survival in all patients, especially in advanced RCC, which is an independent prognostic factor in disease free survival and overall survival. Compared with EZH2, H3K27me3 expression is not an independent prognostic factor. The expressions of H3K27me3 and EZH2 are not completely consistent, which might be due to complicated interaction of Polycomb Repressor Complex 2. A combination of EZH2 expression and TNM stage could have better prognostic value than do TNM stage or EZH2 expression alone in both sets for disease free survival and overall survival.Conclusion:These results imply that evaluating intratumoral EZH2 density might improve prognostic value to the TNM staging system and inform better personalize treatment decisions for patients with late-stage renal cell carcinoma.EZH2 promotes tumor cell migration and invasion via epigenetic repression of E-cadherin in renal cell carcinoma Objective:To investigate the molecular mechanism and clinical significance for an oncogenic role of EZH2 in renal cell carcinoma (RCC).Methods:Immunohistochemistry analyses of EZH2, H3K27me3 and E-cadherin were performed in tumor tissue samples from 257 patients with RCC. Regulatory effects of EZH2 on E-cadherin expression were examined by qRT-PCR, Western blot, ChIP and immunohistochemical staining. Migration and invasion assays were performed in RCC cell lines. Tumor xenograft experiments with RCC cells were carried out in nude mice.Results:EZH2 promotes migration and invasion in RCC cell lines. Silencing EZH2 with shEZH2 or DZNep can inhibit migration and invasion, up-regulate the expression of E-cadherin in vitro, inhibit tumor growth, and prolong survival in vivo. EZH2 expression accompanied with E-cadherin repression appears to be associated with advanced disease stage and lead to poor overall survival and disease-free survival.Conclusion:EZH2 may contribute to RCC progression via repression of E-cadherin and is a potential therapeutic target for advanced RCC.