Glioblastoma (GBM) is a highly aggressive brain cancer with poor patient outcomes. This study uses a multi-step approach to identify reliable genetic markers for the disease. First, we analysed the GSE4290 dataset, comparing 77 tumour samples to 23 healthy brain controls to identify significantly overexpressed genes. To ensure these findings were not specific to a single study, we validated our results using the GSE147352 dataset. Finally, we correlated these gene expression levels with clinical outcomes using survival data from The Cancer Genome Atlas. Our results identified a core set of genes, including topoisomerase II alpha, maternal embryonic leucine zipper kinase, BIRC5 and abnormal spindle-like microcephaly (ASPM), which are consistently upregulated in tumours but do not significantly predict patient survival. These findings provide a validated molecular signature that defines the GBM transcriptome, though its clinical impact appears decoupled from overall survival, likely due to intensive treatment protocols or other dominant biological factors.