Epithelial-To-Mesenchymal Transition and Its Correlation With Clinicopathologic Features in Patients With Urothelial Carcinoma of the Bladder

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Abstract

Micro-Abstract

The present study evaluated the diagnostic and prognostic potential of epithelial-to-mesenchymal transition (EMT) biomarkers in urinary bladder cancer in the clinical setting. Molecular validation of the EMT marker profile and its correlation with a poor clinical outcome make it a sensitive and effective prognostic tool for the objective and systematic investigation of EMT functions in the pathogenesis of urinary bladder cancer.

Introduction:

Epithelial-to-mesenchymal transition (EMT) is a dynamic process in the pathogenesis of urinary bladder cancer. Despite significant advancements in its diagnosis and treatment, the outcomes have more or less remained the same. In the present study, the expression of EMT markers was investigated to evaluate its prognostic significance in patients with non–muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC).

Materials and Methods:

The present study was undertaken to examine the expression of EMT markers, including E-cadherin, N-cadherin, vimentin, Snail, Twist, Zeb, and Slug, on 28 bladder tumor tissues (15 cases of NMIBC and 13 of MIBC) using reverse transcription-polymerase chain reaction. Immunohistochemical (IHC) staining was performed to check the protein expression and localization of E-cadherin, N-cadherin, vimentin, Snail, and Slug.

Results:

At the message level, reduced expression of E-cadherin correlated with gender (P = .004), enhanced expression of N-cadherin correlated with stage and age (P = .02, for both), and increased expression of EMT transcription factors correlated significantly with stage, grade, or age. Inverse correlation of reduced levels of E-cadherin were observed with new expression of N-cadherin (P = .001; Mann-Whitney U test) and vimentin (P = .001; Mann-Whitney U test). On IHC, novel expression of vimentin and N-cadherin was associated with enhanced expression of Snail and Slug (P = .005; Wilcoxon signed rank test).

Conclusion:

Molecular validation of the EMT marker profile proved to be a sensitive and an effective prognostic tool for objective and systematic investigation of EMT function in the pathogenesis of urinary bladder cancer. Nevertheless, further studies are required with a greater number of clinical samples.

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