Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma.

BACKGROUND Hypermethylation of genetic promoters plays an important role in tumorigenesis. This study aimed to identify and validate promoter methylation-drivengenes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC). METHODS Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing PCR (BSP) in paired tumor and normal tissues of 72 PDAC patients.Kaplan-Meier survival analyses were performed to evaluate the clinical value of PMDGs. RESULTS In GSE49149, the β-value of the DPP6promoter was significantly higher in tumor compared with normal samples (0.50 vs 0.24, P < 0.001). In the PDAC cohort of TCGA, the methylation level of the DPP6promoter was negatively correlated with mRNA expression (r = -0.54, P < 0.001). In a multivariate Cox regression analysis, hypermethylation of the DPP6promoter was an independent risk factor for PDAC (HR = 543.91, P = 0.002). The results of BSP revealed that the number of methylated CG sites in the DPP6promoter was greater in tumor samples than in normal samples (7.43 vs 2.78, P < 0.001). The methylation level of the DPP6promoter was moderately effective at distinguishing tumor from normal samples (AUC = 0.74, P < 0.001). Hypermethylation of the DPP6promoter was associated with poor overall (HR = 3.61, P < 0.001) and disease-free (HR = 2.01, P= 0.016) survivals for PDAC patients. CONCLUSIONS These results indicate that DPP6promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma.