Abstract
Background: TEP1 is a ribonucleoprotein complex component that binds to telomerase, and its role in GBM development is unclear. This study was designed to investigate the regulatory mechanism of TEP1 in GBM development. Methods: TEP1 expression was verified using the TCGA and CGGA databases. Kaplan–Meier survival curve, univariate Cox regression, and multivariate Cox regression analyses were employed to assess the prognostic and predictive value of TEP1. KEGG and GO analyses were conducted to identify signalling pathways and functional gene sets enriched in TEP1-related genes. Immune infiltration was evaluated using the CIBERSORT and ssGSEA algorithms. Single-cell sequencing data were utilized to pinpoint TEP1-enriched cell populations. Drug susceptibility data from the CCLE, GDSC, and CTRP databases were integrated to explore potential therapeutic implications. Further validation was performed using immunofluorescence, quantitative real-time PCR, Western blotting, and in vitro and in vivo ferroptosis assays. Results: TEP1 expression was significantly elevated in GBM tissues compared to normal brain tissues, correlating with copy number alterations and poor overall survival. Elevated TEP1 expression correlated with increased tumour malignancy, IDH wild-type status, and radiotherapy resistance. Functional analyses revealed significant associations between TEP1 expression and pathways involved in lipid metabolism, apoptosis, immune response, cell cycle regulation, and ferroptosis. Immune profiling highlighted enrichment of TEP1 in immune cells, particularly plasmacytoid dendritic cells and natural killer T cells. Elevated TEP1 expression was associated with altered sensitivity to various anticancer drugs, notably ferroptosis modulators. In vitro and in vivo experiments confirmed that TEP1 significantly inhibited ferroptosis induced by RSL3, thereby promoting GBM cell survival and tumour progression. Conclusion: Overall, we found that TEP1 is a promising biomarker for GBM and reduces the susceptibility of GBM cells to ferroptosis, providing a novel target for GBM treatment. Supplementary Information: The online version contains supplementary material available at 10.1186/s12935-025-04114-0.