Abstract
Glucose-regulated protein 78 (GRP78) is a member of the heat-shock protein 70 family. We evaluated the expression of GRP78 using tissue microarray-based immunohistochemistry in tumor tissues and adjacent nontumor tissues from 180 pancreatic ductal adenocarcinoma (PDAC) patients. The associations between the expression levels of GRP78, clinicopathological factors, and overall survival were evaluated. The results showed that the expression of GRP78 was significantly higher in PDAC cells than in normal pancreatic duct cells within adjacent nontumor tissues (p < 0.05). The increased expression of GRP78 in the tumor tissues was significantly correlated with a higher T-stage (p < 0.05) and a shorter overall survival (OS, p < 0.05). In an in vitro study, the regulation of GRP78 in the PDAC cell lines affected the proliferation, migration, and invasion of PDAC cells through the regulation of CyclinD1, cyclin-dependent kinase (CDK) 4, CDK6, phospho-signal transducer, activator of transcription 3 (p-STAT3), janus kinase 2 (JAK2), ras homolog gene family member A (RhoA), Rho-associated kinase 1 (ROCK1), and sterile alpha motif domain containing protein 4 (Smad4). The present data suggest that GRP78 plays a crucial role in the proliferation, migration, and invasion of pancreatic cancer cells and may be a suitable prognostic marker in PDAC.
Highlights
IntroductionThe correlation between GRP78 expression and the clinicopathological characteristics of Pancreatic ductal adenocarcinoma (PDAC) and its role in pancreatic cancer have not been reported
We first examined the expression of GRP78 using tissue microarray-based immunohistochemistry on the tumor tissues and adjacent nontumor tissues from 180 patients with Pancreatic ductal adenocarcinoma (PDAC)
We examined the effect of GRP78 expression on prognosis using the Kaplan–Meier method and log-rank test; the univariate analysis showed that the poorer overall survival of patients was significantly associated with high GRP78 expression in the tumor tissues (p = 0 .0077) (Fig. 1J), sex (p = 0 .0075), histologic grade (p = 0 .015), T stage (p = 0.0139), and peripheral nerve infiltration (PNI) (p = 0 .0455) (Table 2)
Summary
The correlation between GRP78 expression and the clinicopathological characteristics of PDAC and its role in pancreatic cancer have not been reported. The correlations between GRP78 expression and the clinicopathological characteristics and overall survival of patients with PDAC were investigated using tissue microarray (TMA)-based immunohistochemistry. The effect of GRP78 expression on the proliferation, migration, and invasion of three PDAC cell lines were evaluated in vitro. The changes in the associated proteins were detected by western blotting
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