Identification of NFE2L2 as a key biomarker associated with pyroptosis in gliomas through bioinformatics and experiments

Glioma is a highly aggressive and recurrent brain tumor, leading to significant impacts on patients’ quality of life and posing substantial economic burdens on healthcare systems because of high mortality rates and long-term treatment costs. Current treatment modalities have limited efficacy and poor prognoses, highlighting the urgent need for novel biomarkers and prognostic models to inform clinical decisions. This study delves into the significance of pyroptosis-related mechanisms in glioma and aims to establish and validate a prognostic model grounded in pyroptosis-related genes. Utilizing a multicenter retrospective analysis coupled with bioinformatics methods, we investigated glioma biomarkers and signatures tied to pyroptosis. We obtained the gene expression profiles of glioblastoma and low-grade glioma (GBM and LGG, hereinafter collectively referred to as glioma for simplicity), which were sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, and analyzed the differentially expressed genes (DEGs). By identifying the intersection between DEGs associated with glioma and pyroptosis-related genes (PRGs), we obtained GBM and LGG pyroptosis-related genes (GBMLGG-PRGs). These GBMLGG-PRGs underwent verification, followed by functional enrichment analysis via cluster and Gene Ontology (GO) analysis. We formulated a model for assessing the risk of prognosis and evaluated its effectiveness. Moreover, key genes were experimentally validated, including the construction of animal models, immunohistochemistry, etc. Our findings revealed 26 GBMLGG-PRGs that serve as prognostic PRGs. Specifically, NFE2L2 was capable of precisely forecasting the survival outcomes of glioma sufferers. NFE2L2 was identified as a key biomarker associated with glioma necrosis. This study reveals the role of pyroptosisrelated genes in gliomas, highlighting potential therapeutic pathways.