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.
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.
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.
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.
From the Departments of *Surgical Oncology,
‡Gastrointestinal Medical Oncology,
§Translational Molecular Pathology, and
∥Molecular and Cellular Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX.
Received for publication July 17, 2018; accepted December 21, 2018.
Address correspondence to: Matthew H. G. Katz, MD, FACS, Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Unit 1484, 1400 Pressler, Houston, TX 77030 (e-mail: firstname.lastname@example.org).
The authors declare no conflict of interest.