Clinical Significance of the Methylated Cytosine-Phosphate-Guanine Sites of Protocadherin-10 Promoter for Evaluating the Prognosis of Gastric Cancer

Abstract

Protocadherin-10 (PCDH10) has been identified as a tumor suppressor gene in multiple carcinomas. In this study, we intended to elucidate the clinical applicability of the methylation of CpG sites of PCDH10 promoter for prognostic prediction in gastric cancer (GC). Qualitative and quantitative detections of PCDH10 promoter methylation were performed with methylation-specific polymerase chain reaction (MSP) and bisulphite genomic sequencing, respectively. The methylated statuses of 27 cytosine-phosphate-guanine (CpG) sites in PCDH10 promoter were detected in a series of 458 GC tissues to supply precise information of prognostic prediction. Associations between molecular, clinicopathologic, and survival data were analyzed. Protocadherin-10 promoter methylation was found in 91.92% in all patients. Gastric cancer patients with 5 or more methylated CpG sites of PCDH10 promoter was significantly associated with poorer survival (p= 0.038). Meanwhile, methylation of combined CpG (-115,-108,-13, and+3) sites was also identified to provide elaborate survival discrimination for GC patients (p= 0.044). On multivariate survival analysis, methylation of combined CpG (-115,-108,-13, and+3) sites (hazard ratio [HR]= 1.255; p= 0.049) was identified to be an independent prognostic indicator of GC, as were N stage and T stage. Additionally, the methylation of combined CpG (-115,-108,-13, and+3) sites had smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) values than the other 2 independent predictors of the survival. Ultimately, we demonstrated that the methylation of combined CpG (-115,-108,-13, and+3) sites was negatively associated with PCDH10 expression in GC tissues. The methylated CpG sites of PCDH10 promoter had significant applicability for clinical evaluation of the prognosis of GC.