Expression and Clinical Significance of Protein Kinase RNA-Like Endoplasmic Reticulum Kinase and Phosphorylated Eukaryotic Initiation Factor 2α in Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Endoplasmic reticulum stress and subsequent phosphorylation of eukaryotic initiation factor 2α (eIF2α) by protein kinase R-like endoplasmic reticulum kinase (PERK) plays an important role in the development and chemoresistance of pancreatic ductal adenocarcinoma (PDAC). However, the expression and significance of phosphorylated eIF2α (p-eIF2α) and PERK in PDAC have not been examined.

METHODS: We examined p-eIF2α and PERK expression in 84 PDAC and paired normal pancreas samples by immunohistochemistry and Western blotting and correlated the results with clinicopathologic parameters and survival.

RESULTS: Mean PERK H score was 140.8 in PDAC compared with 82.1 in normal pancreas (P < 0.001). High p-eIF2α expression was present in 56% of PDACs versus 7.6% of normal pancreases (P < 0.001). High PERK and p-eIF2α expression correlated with shorter overall survival (P = 0.048 and P = 0.03, respectively). By multivariate analysis, high p-eIF2α (P = 0.01), positive margin (P = 0.002), and lymph node metastasis (P = 0.01) were independent prognosticators for survival.

CONCLUSIONS: The expression levels of PERK and p-eIF2α are higher in PDAC than those in normal pancreas. High levels of PERK and p-eIF2α are predictors of shorter survival in PDAC patients, suggesting that PERK and eIF2α could be promising targets in PDAC.