Abstract
BACKGROUND: Accumulating evidence highlights the critical role of palmitoylation in tumorigenesis, including the regulation of oncogenic signaling pathways, metabolic reprogramming, and immune evasion mechanisms. This study was designed to systematically investigate the prognostic significance of palmitoylation-related genes in glioblastoma multiforme (GBM). METHODS: Through comparative transcriptome analysis of GBM and normal brain tissues based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), we identified 343 palmitoylation-related differentially expressed genes (DEGs). Subsequently, 80 candidate genes were extracted from the constructed protein-protein interaction (PPI) network. By applying the machine learning algorithm-least absolute shrinkage and selection operator (LASSO) regression combined with Kaplan-Meier (K-M) survival analysis, we identified core genes significantly associated with patients' overall survival (OS). Furthermore, single-cell RNA sequencing (scRNA-seq) analysis demonstrated that GABRB2, NCF2, and GRIN2A were enriched in critical oncogenic pathways, including MYC targets and KRAS signaling. Meanwhile, they exhibited a significantly heterogeneous expression pattern in GBM. RESULTS: Palmitoylation-related gene expression was higher in GBM tissues than in normal brain tissue. GABRB2 and GRIN2A inhibited the proliferation and migration of GBM cell lines. NCF2 promoted the proliferation and migration of GBM cell lines. CONCLUSIONS: This study was designed to systematically investigate the prognostic significance of palmitoylation-related genes in GBM. GABRB2, NCF2, and GRIN2A are expected to become new biomarkers for GBM.