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

Abstract EN

Emerging evidence indicates that peroxisome proliferator-activated receptor γ (PPARγ) and DNA methyltransferases (DNMTs) play a role in carcinogenesis.

In this study we aimed to evaluate the expression of PPARγ, DNMT1, and DNMT3B and their correlation with clinical-pathological features in patients with pancreatic cancer (PC), and to define the effect of PPARγ 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 PPARγ and DNMT1 levels did not show significant alterations in PC patients.

Expression levels between PPARγ 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 PPARγ and DNMTs appear interrelated in PC, and this interaction might influence cell phenotype and disease behavior.