Correlations among PPAR, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer

Emerging evidence indicates that peroxisome proliferator-activated receptor γ (PPAR γ ) and DNA methyltransferases (DNMTs) play a role in carcinogenesis. In this study we aimed to evaluate the expression of PPAR γ , DNMT1, and DNMT3B and their correlation with clinical-pathological features in patients with pancreatic cancer (PC), and to define the effect of PPAR γ activation on DNMTs expression in PC cell lines. qRT-PCR analysis showed that DNMT3B expression was downregulated in tumors compared to normal tissues ( P = 0.03), whereas PPAR γ and DNMT1 levels did not show significant alterations in PC patients. Expression levels between PPAR γ and DNMT1 and between DNMT1 and DNMT3B were highly correlated ( P = 0.008 and P = 0.05 resp.). DNMT3B overexpression in tumor tissue was positively correlated with both lymph nodes spreading ( P = 0.046) and resection margin status ( P = 0.04), and a borderline association with perineural invasion ( P = 0.06) was found. Furthermore, high levels of DNMT3B expression were significantly associated with a lower mortality in the whole population (HR = 0.485; 95%CI = 0.262–0.895, P = 0.02) and in the subgroup of patients without perineural invasion (HR = 0.314; 95%CI = 0.130–0.758; P = 0.01), while such association was not observed in patients with tumor invasion into perineural structures ( P = 0.70). In conclusion, in vitro and in vivo PPAR γ and DNMTs appear interrelated in PC, and this interaction might influence cell phenotype and disease behavior.