Differentially Expressed Genes Enrichment Analysis of Pancreatic Ductal Adenocarcinoma and Pancreatic Intraepithelial Neoplasia; an In Silico Study

Abstract Introduction/Objective Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death in the United States. Determining the genetic alterations involved in the formation of PDAC and its precursor, pancreatic intraepithelial neoplasia (PanIN), may lead to earlier detection and new therapeutic options. We performed an analysis of the genetic alterations responsible for the progression of the normal pancreatic tissue to PanIN and ultimately from PanIN to PDAC. Methods/Case Report Initially, we used the continuous bioinformatic analysis in such a way that the RNA-seq datasets were extracted from the Biojupies database. We separately analyzed two datasets that included PDAC and PanIN, where their differentially expressed genes (DEGs) were obtained by comparison with controls. A Venn diagram was drawn to visualize the overlapping and non-overlapping DEGs in both groups. Using the Enrichr and ShinyGO databases, we examined the cell signaling pathways and ontologies of up/down-regulated genes. We mapped the protein network of important genes involved in cancer pathways by the STRING database. Finally, the shared and non-shared candidate proteins in the PDAC and PanIN pathways with the GEPIA database were confirmed in human samples. Results (if a Case Study enter NA) We found six shared genes in PDAC and PanIN including RAC1, RAP1A, ITGA5, RHOA, FZD2, and FN1, which appear to take part in the transition of PanIN to PDAC. Our result showed that the aforementioned genes are critical in the cell cycle, angiogenesis, and cell death processes. In the next step, the DEGs analysis in both PDAC and PanIN revealed the role of candidate genes (COX5B, NME2, MGLL, and PAICS for PanIN and PRKCA, PLCG2, NOS3, and PTK2 for PDAC) in cellular aging, MAPK, and PI3K/Akt signaling pathways. Conclusion Our findings showed that the overexpression of RAC1, RAP1A, ITGA5, RHOA, FZD2, and FN1 may have an important role in PanIN shifting to PDAC.