PURPOSE: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and plays an important role in the development and progression of cancer. The current study aimed to elucidate the correlation between HDGF expression, clinic-pathologic parameters, and associated molecular factors of oral cancer.
MATERIALS AND METHODS: The surgically resected samples from a total of 95 patients with oral cancer (squamous cell carcinoma) were enrolled to construct the tissues microarray (TMA) in this retrospective study. The HDGF expression in TMA of oral cancer was determined by immunohistochemistry. HDGF and vascular endothelial growth factor (VEGF) immunostaining in tumor samples was scored and the labeling index were correlated with various clinic-pathologic parameters by statistic analysis.
RESULTS: Expression of nuclear HDGF and VEGF was highly correlated with primary T stage (P=0.004 and P=0.038, respectively) and histological grade (P=0.013 and P=0.017, respectively). VEGF expression also associated with nodal status (P=0.021). Moreover, expression of nuclear HDGF and VEGF were highly correlated to each other (P=0.006). On the other hand, expression of HDGF in cytoplasm only associated with tumor necrosis (P=0.002) and showed no impact on survival. In univariate analysis, high expression of nuclear HDGF and VEGF significantly affected disease-specific, metastasis-free, and local recurrence-free survival. Multivariate analysis also indicated that expression level of nuclear HDGF is an independent prognostic factor for disease-specific and local recurrence-free survival (P=0.028; P=0.0285). Indeed, high expression of VEGF is also an independent factor in disease-specific, local recurrence-free, and metastasis free survival (P=0.0183; P=0.0461; P=0.0153).
CONCLUSION: The data showed that high expression of nuclear HDGF and VEGF in squamous cell carcinoma of oral cavity might identify patients at risk of aggressive disease and predict poor prognosis. HDGF might play as key of regulation of tumorigenesis. Therefore, HDGF could be a candidate gene for the development of diagnostic and therapeutic strategies for oral cancer. Further studies are still need to determine the precise role of HDGF in the biological behavior of oral caner and the regulatory mechanism with other associated molecular factors.