Correlations among PPARγ, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer.
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.
Division and Laboratory of Gastroenterology Unit, "Casa Sollievo della Sofferenza" IRCCS Hospital, Viale dei Cappuccini n.1, 71013 San Giovanni Rotondo, Italy.
Valerio
V
Pazienza
Francesca
F
Tavano
Giorgia
G
Benegiamo
Manlio
M
Vinciguerra
Francesca Paola
FP
Burbaci
Massimiliano
M
Copetti
Fabio Francesco
FF
di Mola
Angelo
A
Andriulli
Pierluigi
P
di Sebastiano