SFXN3 Serves as a Predictive Biomarker for Cisplatin Response and Survival in Head and Neck Squamous Cell Carcinoma

Objective: The systematic evaluation of expansive genomic databases facilitates the discovery of clinically vital biomarkers. While Sideroflexin 3 (SFXN3) consistently displays elevated expression in head and neck squamous cell carcinoma (HNSCC), its specific pathobiological functions and prognostic value remain insufficiently characterized. This study aims to delineate the clinical and functional significance of SFXN3 in HNSCC. Methods: We interrogated SFXN3 expression patterns, patient survival outcomes, and immune cell infiltration characteristics utilizing multiple independent repositories, including the cancer genome atlas (TCGA) and gene expression omnibus (GEO). The prognostic independence of SFXN3 was verified via multivariate Cox regression. These computational findings were subsequently corroborated through targeted in vitro functional assays. Results: SFXN3 expression was significantly augmented in HNSCC, demonstrating strong correlations with advanced disease stages and reduced overall survival. Multivariate models confirmed its status as an independent prognostic indicator. Furthermore, SFXN3 upregulation was closely tied to an immunosuppressive microenvironment. In vitro validations revealed that SFXN3 knockdown substantially impairs cell proliferation while simultaneously sensitizing HNSCC cells to cisplatin-induced apoptosis via intrinsic pathways. Conclusion: Ultimately, SFXN3 represents a robust prognostic indicator and an actionable therapeutic vulnerability to counteract both drug resistance and tumor immune escape in HNSCC.