Background and Aims: Previous studies have shown that DEP domain protein 1B (DEPDC1B) is abnormally expressed in a variety of tumors and plays an important role in tumor progression. However, the expression level and clinical significance of DEPDC1B in pancreatic cancer are still unclear. Therefore, this study was aimed to investigate the clinical significance of DEPDC1B in pancreatic cancer by determining the DEPDC1B expression in pancreatic cancer tissue and its association with the clinicopathologic parameters and prognosis of pancreatic cancer patients.  
Methods: The clinical data of pancreatic cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and then, the DEPDC1B expressions in pancreatic cancer tissue were analyzed, and the relation of DEPDC1B expression with the prognosis of pancreatic cancer patients was determined by Kaplan-Meier survival curve and Cox risk model. The DEPDC1B expression in 97 paired specimens of pancreatic cancer and adjacent normal tissues was detected by immunohistochemical staining, and the associations of DEPDC1B expression with clinicopathologic variables and prognosis were evaluated. 
Results: The DEPDC1B expression of in pancreatic cancer tissue was significantly higher than that in matched normal tissues in TCGA database and the GSE16515, GSE15471 and GSE28735 datasets of GEO database (all P<0.05); the survival time of pancreatic cancer patients with high DEPDC1B expression was significantly shortened in TCGA database and GSE28735 dataset; DEPDC1B expression was an independent risk factor for the prognosis of pancreatic cancer patients in TCGA database (HR=1.32, 95% CI=1.118–1.559, P=0.001). In the 97 clinical pancreatic cancer patients, the positive DEPDC1B expression rate was significantly higher in pancreatic cancer tissue than that normal tissue (69.07% vs. 11.34%, P<0.001); the DEPDC1B expression was significantly associated with the degree of differentiation, clinical stage and lymph node metastasis (all P<0.05); the overall survival of patients with high DEPDC1B expression was shorter than that of patients with low DEPDC1B expression; the DEPDC1B expression was an independent risk factor  for prognosis (HR=1.126, 95% CI=1.012–1.253, P=0.029). 
Conclusion: High DEPDC1B expression may be involved in the occurrence, development and metastasis of pancreatic cancer, and it can be used as a prognostic biomarker for pancreatic cancer patients.