Investigating the potential role of EIF2S2 in OSCC progression through comprehensive bioinformatics analysis and experimental validation.

BACKGROUND: The expression of EIF2S2 in oral squamous cell carcinoma (OSCC) may be closely linked to tumor progression and immune evasion. OBJECTIVE: To explore the expression patterns of EIF2S2 in OSCC and its associations with the immune microenvironment, mutational burden, drug sensitivity, and prognosis. METHODS: We studied the functionality of EIF2S2 through tissue sample analysis, differential expression analysis, single-cell RNA-sequencing (scRNA-seq), immune scoring, drug sensitivity assessments, and interaction network construction. RESULTS: EIF2S2 expression was significantly upregulated in OSCC tissues (AUC = 0.846). There were notable differences in immune scoring, cell infiltration, and functional activity between high and low expression groups. The high expression group exhibited significantly reduced immune cell infiltration (e.g., CD8 + T cells), decreased immune function, and poor responses to CTLA-4 and PD-1 therapies. At the single-cell level, significant changes were observed in the ratios of B cells and T cells in the high expression group. Differential gene analysis revealed significant differences in immune-related genes between the two groups. Mutational analysis showed a higher tumor mutational burden (TMB) in the high EIF2S2 expression group, which correlated with worse prognosis (p = 0.012). Drug enrichment analysis identified several potential drugs associated with EIF2S2, with molecular docking confirming binding patterns. CONCLUSION: EIF2S2 not only promotes tumor progression in OSCC, but may also affect the efficacy of immunotherapy by modulating the immune microenvironment, with its high expression correlating with poor prognosis, suggesting that EIF2S2 may serve as a potential biomarker and therapeutic target.