Aberrant Methylation of CDH13 is a Potential Biomarker for Predicting the Recurrence and Progression of Non-Muscle-Invasive Bladder Cancer

BACKGROUND: CDH13 is a novel tumor suppressor gene often inactivated by aberrant promoter methylation in human cancers. Previous studies have shown that CDH13 methylation correlated with advanced disease and poor prognosis in non-muscle invasive bladder cancer (NMIBC). The aim of the current study was to investigate the correlations between CDH13 methylation and disease recurrence as well as progression of NMIBC. MATERIAL/METHODS: The methylation status of CDH13 in 178 NMIBC samples and 38 normal bladder epithelial tissues was examined by methylation-specific PCR (MSP), and then correlated with clinicopathological features. RESULTS: We found that CDH13 methylation occurs frequently in NMIBC, and significantly correlates with high grade, advanced stage, larger tumor size, and tumor recurrence and progression. Moreover, patients with methylated CDH13 exhibited significantly shorter recurrence-free survival (P<0.0001) and progression-free survival (P=0.0060) than patients with unmethylated CDH13. In addition, a multivariate Cox proportional hazard model analysis suggests that CDH13 methylation is an independent predictor for the recurrence (P=0.0043) and progression (P=0.0016) of NMIBC after initial transurethral resection. CONCLUSIONS: Our findings demonstrate that CDH13 methylation is a frequent event in NMIBC, and is associated with unfavorable tumor features. It should be used as an independent predictor for the recurrence and progression of NMIBC, and may be useful for the design of individualized therapeutic modalities.