Clinicopathological Features and Prognostic Implications of Raf Kinase Inhibitor Protein Downregulation in Tongue Squamous Cell Carcinoma

Abstract

Raf kinase inhibitor protein (RKIP) is recognized as a suppressor of metastasis, and the downregulation of RKIP is associated with aggressive events and a poor outcome in a variety of solid tumors. However, the clinical relevance of RKIP expression in tongue squamous cell carcinoma (TSCC) remains unclear. In the present study, the expression of RKIP in 85 pairs of TSCC and corresponding adjacent non-cancerous tissues, 30 matched metastatic lesions from the cervical lymph nodes and 32 oral leukoplakia samples were assessed using immunohistochemical methods. The association between RKIP expression and clinicopathological features was then evaluated. Kaplan-Meier survival analysis and Cox proportional hazards model were used to estimate the effect of RKIP expression on the survival time of patients with TSCC. The results revealed that RKIP expression was dramatically downregulated in TSCC, and to an even greater extent in metastatic lesions. RKIP downregulation was significantly associated with the presence of lymphatic metastasis and the clinical stage of TSCC. Furthermore, patients with low RKIP expression demonstrated a significantly shorter overall survival time. Multivariate analysis indicated that RKIP expression may be an independent prognostic factor in TSCC. In conclusion, the present findings indicate that the lack of RKIP expression is of clinical significance and may serve as a prognostic biomarker in TSCC.