The assessment of of hypoxic and angiogenetic factors on tumor behavior in larynx cancer

Objective: In larynx cancers, an "ideal" cancer biomarker has not been introduced yet. The purpose of this study was to evaluate the factors associated with hypoxia and angiogenesis in the patients with laryngeal neoplasms and to determine their role as diagnostic, predictive and prognostic candidate biomarker. Method: Patients with benign, premalignant and malignant neoplasms of the larynx were enrolled. Sample blood was taken from all patients before treatment. Hypoxia inducible factor- 1 (HIF-1), -2 (HIF-2), -3 (HIF-3), Vascular Endothelial Growth Factor (VEGF), Osteopontin (OPN) and Matrix metalloproteinase-9 (MMP-9) were measured. Sociodemographic and clinicopathologic information, locoregional recurrence, distant metastasis and survival were recorded in all cases. All data were recorded in SPSS for Mac program and statistical analyzes were performed. A p value of <0.05 was accepted as statistically significant. Results: This study included 12 patients with benign laryngeal neoplasm, 8 patients with premalignant laryngeal neoplasm and 44 patients with malignant laryngeal neoplasm. Serum HIF-1, -2, -3, VEBF, OPN and MMP-9 were not be detected as diagnostic biomarkers for benign, premalignant and malign laryngeal neoplasms. High serum HIF-2 and MMP-9 level negatively affected the oncological outcomes. In addition, Serum HIF-2 (2-year overall survival: HR: 8.59, p=0.021, 2-year disease free survival: HR: 7.76, p=0.027 , 2-year distant metastasis free survival: HR: 7.77, p=0.027, 2-year locoregional control: HR: 8.57, p=0.021) and MMP-9 (2-year overall survival: HR: 7.46, 2-year disease free survival: HR: 7.02, 95% CI: 1.26-39.07, 2-year distant metastasis-free survival: HR: 7.04, 2-year locoregional control: HR: 7.44, p=0.023) were found to be independent prognostic factors. Conclusion: In larynx cancers, serum HIF-2 and MMP-9 may be used as a prognostic biomarker irrespective of treatment modality. Key Words: Larynx Cancer, Hypoxia, Tumor microenvironment, Biomarker, Prognosis, Survival.