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.
Department of Urology, Affiliated Xuzhou Hospital of Jiangsu University (Xuzhou Cancer Hospital), Xuzhou, 221000, China. lylxz2012@126.com.
Ying-Li
YL
Lin
Department of Anesthesiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China. aili1981@126.com.
Yan-Ling
YL
Wang
Department of Urology, Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China. mjg2014sjz@163.com.
Jian-Guo
JG
Ma
Department of Urology, Third Hospital of Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang, 050051, Hebei Province, China. lwp2014sjz@163.com.
Wen-Ping
WP
Li
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019175:DNA Methylation; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D000091363:Protocadherins; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy
D014408:Biomarkers, Tumor; D015820:Cadherins; C115816:PCDH8 protein, human; D000091363:Protocadherins