Abstract
The aim of this study was to examine the expression profile, clinical significance, and potential diagnostic/prognostic value of the long non-coding RNA (lncRNA) SMAD5-AS1 in glioma. METHODS: Expression of SMAD5-AS1 and its associations with survival were analyzed in patients with lower-grade glioma (LGG) and glioblastoma (GBM) using GEPIA2, R, UALCAN, and TIMER3 platforms. RESULTS: SMAD5-AS1 was significantly upregulated in multiple cancers, particularly gliomas (LGG and GBM; P < 0.05), demonstrating strong diagnostic performance for GBM (AUC = 0.87) and moderate performance for LGG (AUC = 0.71). In LGG, high SMAD5-AS1 expression was associated with poorer overall survival (HR = 25.53; P < 0.001) and enrichment in higher-grade tumors and astrocytic subtypes (P < 0.01), suggesting a link to tumor aggressiveness. Furthermore, SMAD5-AS1 expression was negatively correlated with infiltration by immunosuppressive cells, implicating a role in modulating the tumor immune microenvironment. CONCLUSION: SMAD5-AS1 represents a promising diagnostic and prognostic biomarker in glioma, with elevated expression linked to increased tumor aggressiveness, immunosuppression, and adverse patient outcomes.