Identification of novel predictive markers for the prognosis of pancreatic ductal adenocarcinoma.

This study demonstrated that klotho gene expression was significantly lower whereas miR-504 and phospho-IGF-1R levels were significantly higher in PDAC than in normal pancreatic tissues. miR-504 level significantly correlated with klotho mRNA and promoter methylation level in PDACs. Loss of Klotho protein expression, klotho promoter hypermethylation, high miR-504 levels, and high phospho-IGF-1R levels significantly correlated with poor survival, high clinical and pathological stages in PDAC patients. The demethylation reagent and miR-504 inhibitor increased klotho gene expression, invasion, and migration in BxPC-3 and Panc-1 cells. Klotho is a tumor suppressor whose expression in PDAC correlated with progression and prognosis of PDAC.