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To identify cuproptosis-related genes as potential diagnostic, therapeutic, and prognostic biomarkers for glioblastoma (GBM). The GBM GSE16011 dataset was downloaded from the GEO database, and the dataset was subjected to differential gene analysis via Perseus software. Cuproptosis-related genes were obtained from the PubMed database. Venn analysis was used to obtain the cuproptosis-related DEGs (CuDEGs) between the DEGs and the cuproptosis-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore the functions of the CuDEGs, and cluster analysis was performed to assess the similarity of the CuDEGs between the GBM group and the control group. Potential targets were screened through protein-protein interaction (PPI) analysis and the fold change values of differential expression. The expression of potential targets in GBM tissues was validated via the GEPIA database, and survival analysis was used to determine the prognostic value of potential targets. Potential targets and core targets were further verified through analysis of the GSE16011 dataset, Human Protein Atlas (HPA) database, and experimental validation in U87-MG and U251 GBM cells using immunofluorescence and western blot. A total of 39 CuDEGs were obtained from the intersection of 9,849 DEGs and 88 cuproptosis-related genes. GO and KEGG enrichment analyses revealed that the CuDEGs were closely associated with the occurrence and development of GBM. Among the 39 CuDEGs, 11 potential targets with a fold change greater than 1.2 were selected. The expression of 11 potential targets was subsequently validated. Compared with that in the control group, the expression of the 6 upregulated CuDEGs significantly increased in the GBM group. Among the 6 upregulated CuDEGs, VEGFA, LOX, and LOXL1 were significantly different in overall survival (P < 0.05), with high expression correlated with lower survival rates and shorter survival times. However, no significant differences in overall survival were observed for the 5 downregulated CuDEGs. Three upregulated VEGFA, LOX and LOXL1 were selected as potential core targets for GBM. Significant differences in overall survival were shown for these three potential core targets combined, with high expression still associated with lower survival rates and shorter survival times. The expression levels of the three potential core targets were positively correlated with glioma grade, and significant differences were detected in grade IV gliomas compared with other grades in the GEPIA database. Experimental validation confirmed significantly elevated expression of these three genes in GBM cells compared to normal controls. The cuproptosis-related genes VEGFA, LOX, and LOXL1 are highly expressed in GBM and closely associated with tumor progression and poor prognosis, suggesting their potential as core biomarkers for GBM diagnosis, therapy, and prognosis evaluation.