Clinical significance of protocadherin 8 (PCDH8) promoter methylation in non-muscle invasive bladder cancer

BACKGROUND: PCDH8 is a novel tumor suppressor gene, and frequently inactivated by promoter methylation in human cancers. However, there is little information regarding PCDH8 methylation in non-muscle invasive bladder cancer (NMIBC). The aim of this study was to investigate the methylation status of PCDH8 in NMIBC and its clinical significance. METHODS: The methylation status of PCDH8 in 233 NMIBC tissues and 43 normal bladder epithelial tissues was examined by methylation-specific PCR (MSP), and then analyzed the correlations between PCDH8 methylation and clinicopatholocial features. Subsequently, Kaplan-Meier survival analysis and Multivariate Cox proportional hazard model analysis was used to investigate the correlation between PCDH8 methylation and prognosis of patients with NMIBC. RESULTS: PCDH8 methylation occurred frequently in NMIBC tissues than those in normal bladder epithelial tissues. In addition, PCDH8 methylation significantly correlated with advanced stage, high grade, larger tumor size, tumor recurrence and progression in NMIBC. Kaplan-Meier survival analysis revealed that patients with PCDH8 methylated have shorter recurrence-free survival, progression-free survival and five-year overall survival than patients with PCDH8 unmethylated. Multivariate analysis suggested that PCDH8 methylation was an independent prognostic biomarker for recurrence-free survival, progression-free survival and five-year overall survival simultaneously. CONCLUSIONS: PCDH8 methylation may be associated with tumor progression and poor prognosis in NMIBC and may be used as a potential biomarker to predict the prognosis of patients with NMIBC.