SLC2A3 Is a Novel Oncogenic Biomarker and Correlates With Tumor Immune Microenvironment in OSCC

Oral squamous cell carcinoma (OSCC) remains a lethal malignancy with limited treatment options and poor prognostic biomarkers. Here, we systematically investigated the oncogenic role of SLC2A3 through multi-omics analysis and experimental validation. Pan-cancer profiling revealed SLC2A3 overexpression in most cancers, correlating with poor survival outcomes. In OSCC, SLC2A3 expression was significantly elevated compared to normal tissues and robustly associated with advanced disease and reduced survival. Co-expression network analysis identified SLC2A3 as a hub gene in immune-related modules, with functional enrichment implicating leukocyte activation, cytokine signaling, and immune checkpoint pathways. Machine learning approaches further prioritized SLC2A3 as the top prognostic candidate among immune-associated genes. Functional assays demonstrated that SLC2A3 knockdown inhibited OSCC cell proliferation, colony formation, migration, and invasion. Critically, multi-algorithm deconvolution revealed that high SLC2A3 expression correlated with an immune-hot tumor microenvironment (TME). Our results establish SLC2A3 as a dual biomarker, driving tumor aggressiveness while shaping an immunogenic TME, and propose that its therapeutic targeting may improve outcomes in OSCC.