Abstract
BackgroundIn this study, miRNAs and their critical target genes related to the prognosis of pancreatic cancer were screened based on bioinformatics analysis to provide targets for the prognosis and treatment of pancreatic cancer.MethodsR software was used to screen differentially expressed miRNAs (DEMs) and genes (DEGs) downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. A miRNA Cox proportional hazards regression model was constructed based on the miRNAs, and a miRNA prognostic model was generated. The target genes of the prognostic miRNAs were predicted using TargetScan and miRDB and then intersected with the DEGs to obtain common genes. The functions of the common genes were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. A protein-protein interaction (PPI) network of the common genes was constructed with the STRING database and visualized with Cytoscape software. Key genes were also screened with the MCODE and cytoHubba plug-ins of Cytoscape. Finally, a prognostic model formed by the key gene was also established to help evaluate the reliability of this screening process.ResultsA prognostic model containing four downregulated miRNAs (hsa-mir-424, hsa-mir-3613, hsa-mir-4772 and hsa-mir-126) related to the prognosis of pancreatic cancer was constructed. A total of 118 common genes were enriched in two KEGG pathways and 33 GO functional annotations, including extracellular matrix (ECM)-receptor interaction and cell adhesion. Nine key genes related to pancreatic cancer were also obtained: MMP14, ITGA2, THBS2, COL1A1, COL3A1, COL11A1, COL6A3, COL12A1 and COL5A2. The prognostic model formed by nine key genes also possessed good prognostic ability.ConclusionsThe prognostic model consisting of four miRNAs can reliably predict the prognosis of patients with pancreatic cancer. In addition, the screened nine key genes, which can also form a reliable prognostic model, are significantly related to the occurrence and development of pancreatic cancer. Among them, one novel miRNA (hsa-mir-4772) and two novel genes (COL12A1 and COL5A2) associated with pancreatic cancer have great potential to be used as prognostic factors and therapeutic targets for this tumor.
Highlights
In this study, miRNAs and their critical target genes related to the prognosis of pancreatic cancer were screened based on bioinformatics analysis to provide targets for the prognosis and treatment of pancreatic cancer
22 differentially expressed miRNAs (DEMs) were identified from 183 pancreatic ductal adenocarcinoma (PDAC) samples from the The Cancer Genome Atlas (TCGA): 5 were upregulated, and 17 were downregulated (Figure 1A)
A total of 402 differentially expressed genes (DEGs) were identified from the GSE28735 dataset of the Gene Expression Omnibus (GEO): 234 were upregulated, and 168 were downregulated (Figure 1B)
Summary
MiRNAs and their critical target genes related to the prognosis of pancreatic cancer were screened based on bioinformatics analysis to provide targets for the prognosis and treatment of pancreatic cancer. Pancreatic cancer, known as pancreatic ductal adenocarcinoma (PDAC), is a malignancy that frequently appears in the digestive system, and its incidence is on the rise worldwide [1]. In China, PDAC is one of the major tumors whose both incidence and mortality are increasing [3]. The lack of proper treatment methods highlights the importance of the identification of new therapeutic targets for PDAC. As the study of miRNAs has deepened in recent years, an increasing number of miRNAs have been confirmed to be related to the development of cancers, including PDAC [6, 7]. It is of great importance to further clarify how miRNAs affect the pathogenesis, invasion and metastasis of PDAC and to provide novel treatment methods
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