Prognostic significance of metabolic adaptation for hypoxic environment in oral squamous cell carcinoma

Abstract

6082 Background: During tumor growth, tumor adapts the hypoxic environment and increases glycolysis. This metabolic switch is related to the aggressive malignant behavior. We investigated the connection between the biomarkers related to the glycolytic metabolism (HIF-1α, PDK-1, LDH-5) and clinicopathologic characteristics in oral cavity and oropharynx squamous cell carcinoma (SCC). Methods: Eligibility criteria was the patients diagnosed oral SCC, received curative radical resection and had available tissue samples. Immunohistochemical stain of the HIF-1α, PDK-1, and LDH-5 was done. Statistical analysis was performed to compare biomarkers between patients and time point. Results: Overall 74 patients were enrolled and stage grouping of the patients was as follows: stage I, 25 (33.8%) patients; stage II 17 (23.0%); stage III 8 (10.8%); stage IV 24 (32.4%). 25 patients were relapsed and 5-year disease-free survival (DFS) rate was 61.4%. High expression of HIF-1α was related to the advanced T stage (p = 0.029), more invasive tumor (p = 0.003) and tumor recurrence (p = 0.037). High expression of PDK-1 was related to the advanced N stage (p = 0.026) and high expression of LDH-5 was related to the lymphatics invasion (p = 0.028), advanced N stage (p = 0.020) and more invasive tumor (p = 0.015). The high expression of HIF-1α, PDK-1, and LDH-5 showed a significant correlation to each other. 16 (21.6%) patients were highly expressed all three markers. High expression of all three markers correlated with more invasive tumor (p = 0.004) and tumor recurrence (p = 0.017). In survival analysis, high expression of HIF-1α and LDH-5 associated with shorter DFS in log rank test (p = 0.002 and p = 0.016, respectively). High expression of all three markers was also associated with shorter DFS (p = 0.002). In multivariate Cox regression analysis, high expression of all three markers was strong independent prognostic factor for DFS (p = 0.021). Conclusions: The oral SCC which glycolytic metabolism was changed showed a more invasive and aggressive phenotype. Taken together, biomarkers related tumor metabolism may be independent prognostic markers for the DFS in the patients with oral SCC. No significant financial relationships to disclose.