Dysregulation and misfolding of CPA۲protein disturb the proteolysis process in Pancreatic adenocarcinoma:integrated systems biology investigation

Objective: Pancreatic adenocarcinoma (PAAD) has high mortalityand a very poor prognosis. Both surgery and chemotherapyhave a suboptimal therapeutic effect, and this caused a needto find new approaches such as immunotherapy. Therefore, exploringpromising biomarkers for the early diagnosis of PAADand new therapeutic methods is needed urgently. In this study,we performed an integrated bioinformatics and systems biologyinvestigation to evaluate a novel regulatory network in pancreaticductal adenocarcinoma cancer.Materials and Methods: Microarray analysis was performedto find novel dysregulated genes in the pancreatic adenocarcinomasamples. GSE۱۸۳۷۹۵ was analyzed using R Studio. Geneontology analysis was performed by Enrichr. Finding the possibledangerous single nucleotide polymorphisms (SNPs) in the۳'UTR region of selected genes was performed by miRNASNP.Protein- Protein interaction analysis was performed by theSTRING online database. Finding possible mutations based onSIFT online database.Results: Microarray analysis revealed that CPA۲ has a significantdown-regulation in the pancreatic adenocarcinoma samples,compared to the control (logFC: -۲.۱۷۰۶۸, adj. P. Value< ۰.۰۰۰۰۱). Based on gene ontology analysis, CPA۲ contributedto the proteolysis process and metallocarboxypeptidaseactivity. From all of the extracted SNPs on the Target gain withSNP, rs۱۴۳۷۵۲۴۴۵۹ can cause a connection with hsa-miR-۳۲۶in the ۳'UTR region CPA۲. Protein-protein interaction analysisrevealed that CPA۲ has significant interaction with CELA۳B(R: ۰.۹۲). Based on SIFT database, rs۷۶۵۰۹۸۶۴ SNP caused themutation of a Glutamic Acid into a Lysine at position ۱۵۴. Thedifference in charge will disturb the ionic interaction made bythe original, wild-type residue.Conclusion: Protein CPA۲ regulates cell proliferation in pancreaticductal adenocarcinoma cancer patients. CPA۲, as a potentialoncogene, has a significant down-regulation in PAADcancer samples. The high amount of CPA۲ has a significant effecton the survival rate of pancreatic ductal adenocarcinomacancer patients and SPINT۱ interaction

Keywords:

Systems Biology , Microarray analysis , Pathway enrichment , Pancreatic adenocarcinoma , CPA۲