In-silico identification of therapeutic targets in pancreatic ductal adenocarcinoma using WGCNA and Trader

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy, accounting for over 90% of pancreatic cancers, and is characterized by limited treatment options and poor survival rates. Systems biology provides in-depth insights into the molecular mechanisms of PDAC. In this context, novel algorithms and comprehensive strategies are essential for advancing the identification of critical network nodes and therapeutic targets within disease-related protein-protein interaction networks. This study employed a comprehensive computational strategy using the metaheuristic algorithm Trader to enhance the identification of potential therapeutic targets. Analysis of the expression data from the PDAC dataset (GSE132956) involved co-expression analysis and clustering of differentially expressed genes to identify key disease-associated modules. The STRING database was used to construct a network of differentially expressed genes, and the Trader algorithm pinpointed the top 30 DEGs whose removal caused the most significant network disconnections. Enriched gene ontology terms included “Signaling by Rho GTPases,” “Signaling by receptor tyrosine kinases,” and “immune system.” Additionally, nine hub genes—FYN, MAPK3, CDK2, SNRPG, GNAQ, PAK1, LPCAT4, MAP1LC3B, and FBN1—were identified as central to PDAC pathogenesis. This integrated approach, combining co-expression analysis with protein-protein interaction network analysis using a metaheuristic algorithm, provides valuable insights into PDAC mechanisms and highlights several hub genes as potential therapeutic targets.