Identification of Potential Therapeutic Targets and Biomarkers for Glioblastomas Through Integrative Analysis of Gene Expression Data

Abstract

Background: In this study, we conducted a comprehensive analysis of differential gene expression data from studies GSE15824 and GSE4290 to identify up-regulated hub genes with potential as therapeutic targets for glioblastomas. Results: Ten up-regulated hub genes, TYROBP, C1QA, C1QB, TLR2, C1QC, CD163, VSIG4, ITGB2, VEGFA, and CD14, were identified. Among them, VEGFA was selected for virtual screening, leading to the discovery of six significant hits. Three hits were from the ChemDiv library of kinase inhibitors (D491-4259, J094-0246, D491-4785), and three from the ZINC20 database (ZINC57658, ZINC57652, ZINC57679), showing promising properties for drug discovery. Furthermore, two drugs for repurposing, Sunitinib and Ticlopidine hydrochloride, were identified. All the hits outperformed control drugs Irinotecan, Carboplatin, and Fluorouracil. Additionally, we identified down-regulated hub genes VAMP2 and ANK3 as potential biomarkers for glioblastomas. Enrichment analysis provided further insights into the molecular pathways involved, shedding light on potential therapeutic strategies for the treatment of glioblastomas. Conclusion: This computational study sheds light on potential drug candidates for glioblastoma treatment and offers valuable insights into the disease's molecular mechanisms, paving the way for improved therapeutic strategies.