Olfactomedin 1 acts as a tumor suppressor in glioblastoma: integrated analysis and mechanistic prediction

Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis, yet its molecular mechanisms remain incompletely understood. Olfactomedin 1 (OLFM1), a member of the olfactomedin-domain-containing protein family, is known for roles in neurodevelopment and is dysregulated in several cancers; however, its function in GBM is unclear. This study aimed to elucidate the potential role of OLFM1 in GBM progression and to explore its underlying molecular mechanisms. Through artificial neural networks, Mendelian randomization, transcriptomic analysis, and experimental validation, we identified OLFM1 as a potential tumor suppressor, with high expression predicting better survival in GBM. The immune infiltration analysis suggested a potential role of OLFM1 in inhibiting macrophage polarization from the M0 to M2 phenotype. Gene set enrichment analysis (GSEA) revealed that high OLFM1 expression is associated with downregulation of the JAK-STAT3 signaling pathway. Experimental assays confirmed that OLFM1 overexpression downregulates JAK-STAT3 signaling. Additionally, drug prediction using DSigDB and molecular docking suggested rosuvastatin as a candidate OLFM1-related GBM inhibitor with strong binding affinity to key pathway proteins. Collectively, our findings indicate OLFM1 as a potential prognostic biomarker and therapeutic target.