Effects of serum HIF-1α, VEGF, and uPA levels on clinicopathologic findings and prognosis in oral squamous cell carcinoma.

Objective: To determine circulating levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and urokinase-type plasminogen activator (uPA) in the peripheral blood of patients with oral squamous cell carcinoma (OSCC) and to explore their relationship with clinicopathologic features and prognosis, in order to facilitate treatment.

Methods: 160 OSCC patients and 51 control subjects were prospectively recruited, and serum HIF-1α, VEGF, and uPA levels were measured by enzyme-linked immunosorbent assay (ELISA). Preoperative threshold values of HIF-1α, VEGF, and uPA were determined by ROC curves. Kaplan-Meier curves were analyzed for overall survival and progression-free survival of patients. Univariate and multivariate Cox risk regression analyzed prognostic factors.

Results: Serum HIF-1α, VEGF, and uPA were higher in OSCC patients compared to control subjects (P < 0.001). Critical values of HIF-1α, VEGF, and uPA were 99.8 pg/mL, 130.4 pg/mL, and 142.9 pg/mL, respectively. Serum levels of HIF-1α, VEGF, and uPA were associated with the overall pathologic status (TNM staging), neural invasion, extranodal extension, lymphovascular invasion, depth of invasion, and degree of cellular differentiation (P < 0.05). Patients with higher serum HIF-1α, VEGF, and uPA levels had poorer overall survival and shorter progression-free survival. Higher-than-threshold serum HIF-1α, VEGF, and uPA were independent prognostic factors for overall survival (P < 0.001, P < 0.001, P = 0.006) of and progression-free survival (P < 0.012, P < 0.001, P = 0.010).

Conclusion: Higher circulating levels of HIF-1α, VEGF, and uPA were associated with clinicopathologic correlations of lymph nodes, metastasis, and were independent risk factors for survival and progression-free survival.