Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma

Aims: We evaluated the association of ligand cyclophilin A (CypA) and receptor CD147 with hypoxia, angiogenesis, lymph node metastasis and prognosis of patients with tongue squamous cell carcinoma (TSCC). Methods and results: We studied the expression of CypA, CD147, hypoxia-inducible factor 1 alpha (HIF-1 alpha), vascular endothelial growth factor A and C (VEGF-A and VEGF-C) protein by immunohistochemistry in 80 specimens of TSCC. CypA, CD147, HIF-1 alpha, VEGF-A and VEGF-C were overexpressed in TSCCs, and were significantly higher than those in normal oral mucosa tissues (P < 0.01). Increased ligand CypA and receptor CD147 correlated significantly with expression of HIF1 alpha, VEGF-A and VEGF-C. A significant relationship between VEGF-A and VEGF-C was also detected (P < 0.01). Patients with overexpression of CypA, CD147, HIF-1a and VEGF-C had significantly worse overall survival (P < 0.05) using Kaplan-Meier analysis. Multivariate Cox regression analysis showed that HIF-1a, recurrence and distant metastasis were independent prognostic factors on overall survival in TSCC patients. Conclusions: The association of expression of ligand CypA and receptor CD147 with carcinogenesis, hypoxia, angiogenesis, metastasis and prognosis of TSCC suggests that ligand CypA and receptor CD147 may have prognostic value and could be regarded as potential therapeutic targets in TSCC.