Background and Aims: UDP-glucose 6-dehydrogenase (UGDH) is a metabolic enzyme that converts UDP-glucose to UDP-glucuronic acid, it affects the tumor invasion and drug resistance by participating in the biosynthesis of glycosaminoglycan in tumor tissues. A number of studies have shown that UGDH gene is involved in the occurrence and development of a variety of cancers. However, there is still no research concerning the UGDH gene in pancreatic cancer, so this study was conducted to investigate the UGDH gene expression in pancreatic cancer and its significance by bioinformatics approaches. 
Methods: The differential expression of UGDH gene in pancreatic cancer tissue was analyzed in 4 data sets of the Oncomine database. Survival analysis was performed based on the gene expression profiles and survival data of the pancreatic cancer in TCGA database. Based on UALCAN database, the correlation between the expression of UGDH gene and other genes in pancreatic cancer in TCGA was analyzed, and the genes with significant positive and negative correlation with UGDH gene were obtained by Pearson coefficient method, and then, GO and KEGG pathway enrichment analyses were performed, respectively. Based on the annotation of the whole human genome from HGNC database, the expression profile of all mRNA in pancreatic cancer was extracted, and then the gene base enrichment analysis of UGDH gene in pancreatic cancer was carried out by using GSEA analysis software; the monogenic PPI network involving the UGDH gene was constructed by GeneMANIA, and the genes appeared in the network were further enriched by Metascape, and then, the critical subnetworks were identified by Cytoscape MCODE plug-in. 
Results: UGDH gene expression was significantly up-regulated in pancreatic cancer samples, and the overall survival rate was significantly higher and survival time was significantly longer in patients with low UGDH gene expression than those in patients with high UGDH gene expression (all P<0.05). GO enrichment analysis found that UGDH and its co-expressed genes were enriched in the endomembrane system organization, RNA localization, proteasomal protein catabolic process, nucleocytoplasmic transport, nucleic acid transport and other biological processes related to cancer. KEGG enrichment analysis showed that the differential expressed genes were mainly enriched in cancer-related pathways such as protein processing in endoplasmic reticulum, autophagy-animal, ubiquitin mediated proteolysis, protein export, spliceosome, RNA transport, mRNA surveillance pathway, viral carcinogenesis, long-term depression, colorectal cancer, N-Glycan biosynthesis, pancreatic cancer and sphingolipid signaling pathway, proteoglycans in cancer, renal cell carcinoma, human cytomegalovirus infection, hepatitis B. GSEA analysis showed the enriched cancer-related pathways such as ubiquitin mediated proteolysis, amino sugar and nucleotide sugar metabolism, aminoacyl-tRNA biosynthesis, oocyte meiosis, renal cell carcinoma, basic transcription factors, sphingolipid metabolism, ErbB signaling pathways, adherens junction, chronic myeloid leukemia, RIG-I like receptor signaling pathway, GNRH signaling pathway, insulin signaling pathway, endometrial cancer, glioma, neurotrophin signaling pathway, MAPK signaling pathway, pancreatic cancer. PPI prediction and key sub-network analysis revealed that HGS, UBE2V1, MAT2A and SUMO1 played important roles in the interaction network. 
Conclusion: UGDH gene expression is up-regulated in pancreatic cancer tissue, and is closely related to the occurrence and development as well as the prognosis of pancreatic cancer. The results of this study may provide important information and basis for future studies on the pathogenesis and molecular target therapy of pancreatic cancer.