Identification of CXCL8, IL1A, and IL1B as Hub Genes of Therapeutic Resistance in Glioblastoma Multiforme via Bioinformatics Analysis

Glioblastoma multiforme (GBM) is a highly aggressive, treatment-resistant brain tumor with a dismal prognosis, and identifying key molecules involved in its therapeutic resistance is essential to improve patient outcomes. This study was undertaken to identify hub genes associated with the radioresistance and temozolomide (TMZ) resistance of GBM using bioinformatics analysis.

RNA-seq and microarray datasets from the GEO database were analyzed to identify differentially expressed genes (DEGs). GO and KEGG pathway enrichment analyses were performed using Enrichr. A protein-protein interaction (PPI) network was constructed using STRING and visualized with Cytoscape, and hub genes were identified by MCODE analysis. Expression and survival analyses were conducted on TCGA and GTEx datasets using GEPIA2.

Twenty-four DEGs were considered linked to radioresistance and 122 to TMZ resistance. Functional enrichment and PPI network analyses highlighted key therapeutic resistance pathways, including cytokine-mediated signaling and inflammatory response pathways. Notably, CXCL8, IL1A, and IL1B were identified as key hub genes significantly enriched in these pathways. Expression analysis confirmed their up-regulation in GBM, and survival analysis indicated their association with prognosis.

This study identifies CXCL8, IL1A, and IL1B as potential therapeutic targets for overcoming the resistance of GBM to radiotherapy and chemotherapy. In addition, these genes might serve as prognostic biomarkers and key regulators of GBM malignancy. Future studies are warranted to explore their functional roles in vivo and assess their potential use as therapeutic intervention targets.