Oral squamous cell carcinoma (OSCC) is the most common epithelial malignancy affecting the oral cavity, and it is especially significant in Asian countries. Patients diagnosed with OSCC have an unfavorable prognosis and additional prognostic markers would help improve therapeutic strategies. We sought to investigate the association between eukaryotic translation initiation factor 5A2 (EIF5A2) and epithelial–mesenchymal transition (EMT) markers as well as the prognostic significance of EIF5A2 in OSCC. The expression of EIF5A2 and EMT markers was measured through the immunohistochemical staining of specimens from 272 patients with OSCC. In addition, the correlation between different clinicopathological factors and EIF5A2 expression was analyzed. The prognostic role of EIF5A2 was then analyzed via Kaplan–Meier analysis and Cox proportional hazard models. Among the 272 patients, high EIF5A2 expression was significantly associated with an advanced N value (p
= 0.008). High tumor expression of EIF5A2 was prone to the expression of low E-cadherin and high beta-catenin (p
= 0.046 and p
= 0.020, respectively). Patients with high EIF5A2 expression had unfavorable five-year survival rates as compared with those with low expression (49.7% and 67.3%, respectively). The prognostic role of EIF5A2 was further confirmed through multivariate analysis (hazard ratio = 1.714, 95% confidence interval: 1.134–2.590, p
= 0.011). High EIF5A2 expression is associated with an advanced N value and EMT markers and may serve as a marker for an unfavorable prognosis in patients with OSCC.
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