BACKGROUND: Oral squamous cell carcinoma (OSCC) remains a clinically heterogeneous malignancy with unsatisfactory long-term outcomes, particularly in patients with advanced disease and treatment resistance. Conventional clinicopathologic parameters incompletely capture the biological diversity of OSCC and provide limited guidance for individualised therapeutic stratification. METHODS: We performed an integrated transcriptomic analysis of TCGA-derived OSCC data to construct and evaluate an immune-associated prognostic signature. Associations with survival, clinicopathologic features, immune infiltration, somatic mutation profiles and pathway-level biological programs were assessed. The manuscript-specified ten-gene equation was additionally evaluated without refitting in an independent CPTAC oral-cavity SCC cohort using overall survival, Harrell's C-index and time-dependent ROC analysis. Amphiregulin (AREG) was selected for functional investigation using siRNA-mediated knockdown, proliferation assays, cisplatin sensitivity testing, IC50 estimation and apoptosis analysis in OSCC cells. RESULTS: The original TCGA analysis separated survival groups and reported 1-, 3- and 5-year AUCs of 0.701, 0.693 and 0.623. In 42 independent CPTAC patients with 14 deaths, however, the fixed score was not significantly associated with overall survival (HR per SD, 1.181; 95% CI, 0.674-2.069; p = 0.561). The C-index was 0.521, and the 1- and 3-year AUCs were 0.369 and 0.550; 5-year evaluation was unsupported by follow-up. The supplied AREG experiments suggested reduced proliferation and increased cisplatin sensitivity after knockdown. CONCLUSIONS: This study identifies an exploratory immune-associated score and AREG-associated cellular phenotypes in OSCC.