Hyperexpression of EMT factors is associated with tumor aggressiveness and worse overall survival in pancreatic cancer patient

Abstract

Objective It has been suggested that Epithelial-mesenchymal transition (EMT) program might be associated with carcinogenesis of pancreatic adenocarcinoma. Furthermore it has been described the association between ZEB1 and worse survival of PDAC patients. However the post-transcriptional regulation pathways remain unclear as well as the role of other EMT-TFs. The purpose of our study to determine the association of EMT-TFs expression with clinicopathological parameters and prognosis of PDAC. Methods Data of 45 patients following pancreatoduodenectomy for PDAC between 2009- 2017 were analyzed. Patient’s mRNA expression levels of Snail1, Snail2, ZEB1, ZEB2 and TWIST in PDAC were compared with normal pancreatic tissue. The correlations among EMT-TFs and HuR as well as clinicopathological parameters were analyzed. The Kaplan-Meier method and log-rank tests were used for univariate analysis. Results Snail1, Snail2, ZEB1 and Twist expression were accordingly 1643.05 fold, 2186.02- fold, 1723.33-fold and 3.72-fold higher, while ZEB2 expression were 0.53-fold lower when compared to normal pancreatic tissue. Univariate analysis revealed that high expression of all EMT-TFs was associated with worse overall survival (0S) of PDAC patients. High expression levels of ZEB1 were associated with peripancreatic invasion. Conclusions Hyperexpression of EMT-TFs is associated with more aggressive clinicopathological features of pancreatic cancer and worse overall survival.