Identification of hub genes and key pathways targeted by miRNAs in pancreatic ductal adenocarcinoma: MAPK3/8/9 and TGFBR1/2

Abstract

Ductal adenocarcinoma of the pancreas(PDAC) is one of the malignancies with the worst prognosis still among solid tumors. Local and distant spread is observed at the time of diagnosis in a very significant part of patients. In recent years, significant improvements have been made in pancreatic cancer surgery, and serious decreases in morbidity and mortality rates have been detected, especially in specific centers. Studies on target gene therapy in all types of cancer, including pancreatic cancer, are very laborious and costly. For this reason, it provides convenience for research aimed at determining clinical markers by using bioinformatics software. In this study, it was aimed to determine the target gene and pathway by performing transcriptome analysis of 14 control and 28 PDAC data belonging to GSE123377 and GSE 163031. As a result of the analysis, it was found that 49 genes were in direct interaction with PDAC by determining the targets of 46 miRNAs with DIANA Path, whose expression differences were determined as a result of the analysis. Based on the PPI topological analysis, it was determined that 46 miRNAs of prostate cancer directly target 12 hub proteins (BRAF, STAT3,TGFBR1,SMAD2,SMAD3, TP53, TGFBR2, KRAS, MAPK1,MAPK3, MAPK8 and MAPK9). Functional Enrichment Analysis and biological process; cell communication with 59.18% and signal transmission with 73.47%; It was observed that protein serine/ threonine kinase activity in molecular function was associated with a 22.45% effect on pathways. Thus, it is planned to support research by providing a system-level view by processing data networks for potential diagnostic biomarkers and target gene therapy for early diagnosis of PDAC.