The Significance Of CDH13Expression And Promoter Methylation In Bladder Cancer

Objective:To investigate the expression of CDH13in bladder transitional cell carcinoma tissues and its relationship with clinicopathologic features as well as patients’prognosis, so as to provide theoretical basis and research base for the diagnosis, assessment of malignant behavior of bladder cancer and patients’prognosis. To investigate the promoter methylation status of CDH13in bladder transitional cell carcinoma tissues, and correlated with its expression status in the first part of the study, so as to explore the correlation between CDH13methylation and its expression; then study the relationship between CDH13methylation and the development of bladder transitional cell carcinoma as well as patients’prognosis, so as to provide novel biomarker for the diagnosis, monitoring and prognosis of bladder transitional cell carcinoma. To study the effects on cell proliferation, migration and invasion of5637cells after CDH13was specifically inhibited by RNA interference.Methods:The expression of CDH13in37normal bladder mucosa and113bladder transitional cell carcinoma tissues was detected using immunohistochemical study, and correlated with tumor number, size, shape, recurrence, grade, stage and patients’ age, gender and prognosis.The methylation status of CDH13in113bladder transitional cell carcinoma and37normal bladder mucosa tissues was detected by Methylation-specific PCR, and then associated with its expression status so as to illustrate the relationship between CDH13methylation and its expression, next correlated CDH13methylation with tumor number, size, shape, recurrence, grade, stage and patients’ age, gender and prognosis. To Silence CDH13expression in5637bladder cancer cells by CDH13siRNA transfection, and confirming the silencing effect using fluorescence quantitative PCR and western blot, and then detecting the effects on the cell proliferation, migration and invasion using MTT cell proliferation assay, Trans well migration and invasion assay.Results:(1) The expression of CDH13was reduced in bladder transitional cell carcinoma tissues compared with normal bladder mucosa tissues and the difference was statistically significant. Decreased expression of CDH13was correlated with tumor growth, recurrence, poorly differentiated and tumor invasion closely, but not associated with tumor number, shape or age and sex of the patients. In addition, the5-year overall survival rate of53patients with CDH13expression normally was86.7%(46/53), but the5-year overall survival rate of60patients with receded CDH13expression was68.3%(41/60), the difference was statistically significant.(2) The methylation rate CDH13in bladder transitional cell carcinoma tissues was54.8%, however no methylation was found in normal bladder mucosa tissues, and the difference was statistically significant. CDH13methylation was negatively correlated with is expression in bladder transitional cell carcinoma tissues. In addition, CDH13methylation was correlated with tumor growth, recurrence, poorly differentiated and tumor invasion as well as poor prognosis of patients closely, but not associated with tumor number, shape or age and sex of the patients.(3) CDH13expression was reduced significantly in5637cells after CDH13-siRNA transfection, and the proliferation, migration and invasion capacity of the cells was enhanced compared with blank and negative control cells, the difference was statistically significant.Conclusion:The reduction of CDH13expression in bladder transitional cell carcinoma tissues was correlated with tumor growth, recurrence, poor differentiation, invasion and poor prognosis of patients closely; these results indicated that reducing expression of CDH13contributed to the development of bladder cancer and poor prognosis of patients. CDH13methylation was negatively correlated with its expression in bladder tranisital cell carcinoma tissues, DNA methylation is the main reason for the reducing of CDH13expression. Moreover CDH13methylation was correlated with tumor growth, recurrence, poorly differentiated and tumor invasion as well as poor prognosis of patients closely; these the results suggested that CDH13methylation may be a novel biomarker for the development of bladder cancer as well as poor prognosis of patients. CDH13expression was specifically inhibited by CDH13siRNA in5637cells, and proliferation, migration and invasion capacity was increased after transfection; these results indicated that reducing expression of CDH13is associated with malignant behaviors of bladder cancer, and it’s an important factor for the development of bladder cancer...