DLC-1 is a candidate biomarker methylated and down-regulated in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies in humans, and its prognosis is generally poor even after surgery. Many advances have been made to understand the pathogenesis of PDA; however, the molecular mechanisms that lead to pancreatic carcinogenesis are still not clearly understood. The aims of this study were to investigate the relationship between DLC-1 methylation status and clinicopathological characteristics of PDA patients and evaluate the role of DLC-1 methylation status in PDA. The expression of DLC-1 mRNA in PDA tissues was analyzed by real-time PCR. The methylation status of DLC-1 was analyzed by methylation-specific polymerase chain reaction (MSP). Furthermore, we determined the prognostic importance of DLC-1 methylation status in PDA patients. Our results showed that the expression level of DLC-1 mRNA in PDA tissues was lower than that in non-cancerous tissues. The rate of DLC-1 promoter methylation was significantly higher in PDA tissues than in adjacent non-cancerous tissues (p < 0.001). Downregulation of DLC-1 was strongly correlated with promoter methylation (P = 0.003). The presence of DLC-1 methylation in PDA tissue samples was significantly correlated with clinical stage (P = 0.005), histological differentiation (P = 0.05), and lymph node metastasis (P = 0.006). Kaplan-Meier survival analysis showed that DLC-1 methylation status was inversely correlated with overall survival of the PDA patients. Further, Cox multivariate analysis indicated that DLC-1 methylation status was an independent prognostic factor for the overall survival rate of PDA patients. In conclusion, our data suggest that downregulation of DLC-1 may be explained by DNA methylation; DLC-1 may be a biomarker for PDA.