SFXN1 expression analysis in oral squamous cell carcinoma and its association with the PI3K-AKT-mTOR pathway and immune cell infiltration

Background: Oral squamous cell carcinoma (OSCC) is a predominant malignancy characterized by aggressive progression and poor prognosis. This study investigated the role of SFXN1 (Sideroflexin 1), a mitochondrial serine transporter, in OSCC using integrated bioinformatic and experimental approaches. Objective: To analyze the expression, clinical relevance, and functional associations of SFXN1 in OSCC through comprehensive bioinformatic and in vitro investigations. Methods: Transcriptomic data from TCGA pan-cancer cohorts were analyzed to evaluate SFXN1 expression patterns. The expression levels in OSCC were validated using KB OC cell lines, with clinical correlations assessed for tumor grade, nodal status, and patient survival. Immune infiltration associations and protein‒protein interaction networks were constructed, followed by pathway enrichment analyses. Experimental validation was performed via in vitro assays. Results: The results revealed that SFXN1 was significantly overexpressed in head and neck squamous cell carcinoma and markedly upregulated in KB cells compared with controls. SFXN1 expression was associated with tumor grade and nodal metastasis, although no significant stage-specific differences were observed. Survival analysis revealed no statistically significant association with overall survival. Immune infiltration analysis indicated modest but significant correlations between SFXN1 and immune cell populations, particularly CD4⁺T cells. Protein network analysis identified hub genes, including AKT1, BCL2, MTOR, and CASP3. Pathway enrichment implicated SFXN1 is involved in the PI3K-AKT-mTOR and p53 signaling pathways. Conclusion: These findings highlight the involvement of SFXN1 in cancer-related pathways and its potential role in OSCC, suggesting potential therapeutic targeting opportunities that need further investigation.