The expression and significance of heparanase in oral squamous cell carcinoma with different metastatic potentials

Abstract

Objective: To detect the expression of heparanase (HPSE) in oral squamous cell carcinoma (OSCC) with different metastatic potentials and investigate its clinical significance. Methods: Transcriptional and translational status of HPSE in OSCC cell lines with different metastatic capacities, primary OSCC samples and their paired metastatic cancer tissues were determined using real-time polymerase chain reaction (PCR) and Western blotting analysis. Immunohistochemistry was used to evaluate HPSE expression in 131 OSCC samples. The correlation between HPSE expression pattern and clinicopathological parameters and clinical outcome in patients with OSCC were analyzed. HPSE level was reduced using HPSE-siRNAs in OSCC cell lines and its impact on cell migration and invasion was measured by scratch assay and matrigel invasion assay. Results: The mRNA and protein levels of HPSE were remarkably up-regulated in OSCC cell lines with highly metastatic capacity (P<0.000 1) and metastatic OSCC tissues (P<0.000 1). The protein levels of HPSE were strongly associated with lymph node metastasis (P<0.000 1) and tumor node metastasis stage (P=0.012). Survival analyses revealed that high HPSE expression was associated with worse overall survival (P=0.000 3). Multivariate Cox proportional analyses indicated that HPSE expression was strongly associated with clinical outcome in patients with OSCC (HR=2.203, 95% CI: 1.203-3.988, P=0.009). The siRNA-mediated silencing of HPSE could suppress the migration and invasion (P=0.008) of HN12 cells in vitro. Conclusions: The up-regulation of HPSE contributes to invasion and metastasis of OSCC. HPSE may serve as a useful biomarker for patients with OSCC.