Abstract
BackgroundPCDH8 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.MethodsThe 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.ResultsPCDH8 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.ConclusionsPCDH8 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.
Highlights
PCDH8 is a novel tumor suppressor gene, and frequently inactivated by promoter methylation in human cancers
Studies reported that protocadheins often inactivated by promoter methylation in human cancers, and the aberrant promoter methylation can be used as potential biomarker for tumor diagnosis, surveillance, or prognosis, such as PCDH8, PCDH10, PCDH17, and PCDH20, which are considered as tumor suppressor genes in tumors [11,12,13,14,15,16,17,18,19,20,21]
We found that PCDH8 methylation occurred in 128 (54.9%) patients with non-muscle invasive bladder cancer (NMIBC) (Figure 1)
Summary
PCDH8 is a novel tumor suppressor gene, and frequently inactivated by promoter methylation in human cancers. Most of the newly diagnosed bladder tumors are non-muscle invasive bladder cancer (NMIBC), the majority of these NMIBC cases will relapse after curative transurethral resection, and some will progress to muscle invasive disease ineluctably [5,6]. The inactivation of PCDH8 caused by promoter methylation has been reported in human cancers, including bladder cancer [13,14,15,16]. We found that PCDH8 promoter methylation occurs frequently in bladder cancer, and associates with poor outcomes of bladder cancer patients [13]. Our previous study included both non-muscle invasive and muscle invasive disease, and the clinical significance of PCDH8 promoter methylation in NMIBC remains largely unclear
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