The Expression of Hypoxia-Related Biomarkers: A Significance of HIF-1 alpha C1772T Polymorphism as Predictor of Laryngeal Carcinoma Relapse

Cancer control : journal of the Moffitt Cancer Center(2022)

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摘要
IntroductionThe association between the expression of HIF-1 alpha in the laryngeal carcinoma and the prognosis of disease is quite well documented, but the significance of HIF-1 alpha C1772T polymorphism and its relation to disease phenotype have to be clarified. The aim of this study was to investigate the influence of C1772T polymorphism on the clinical-pathological characteristics and disease-free survival after initial surgical treatment of patients with laryngeal carcinoma.Materials and methodsThe prospective cohort study included 65 patients with laryngeal carcinoma. Two representative tumor tissue specimens were taken in each patient during surgery; 1 specimen was used to asses HIF-1 alpha C1772T polymorphism and the other 1 to determine the immunohistochemical expression of HIF-1 alpha, VEGF, as well as CD 34 proteins. The comparison of polymorphism frequency between study and control population was conducted by collecting a 5 mL of peripheral venous blood samples in each subject.ResultsClinicopathological characteristics of laryngeal carcinoma didn't affect the expression of hypoxia-related biomarkers, such as HIF-1 alpha, VEGF or MVD. The statistically significant association between HIF-1 alpha and VEGF expression was found (P = .034), but not between HIF-1 alpha expression and MVD value (P = .696). The expression of HIF-1 alpha was significantly higher among CT heterozygotes (P = .029). We found a significantly more recurrence among CT heterozygotes compared with patients with CC homozygous alleles (57.10% and 24.30%, respectively; P = .007). Patients with C1772T polymorphic variants had significantly worse disease-free survival compared with patients without polymorphism (Log-rank test, P = .007).ConclusionHIF-1 alpha C1772T polymorphism was significantly associated with worse disease-free survival which nominates it as a predictor of laryngeal carcinoma relapse. The preoperative assessment of hypoxia-related biomarkers should be used in everyday practice in order to determine the treatment modalities for laryngeal carcinoma.
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关键词
laryngeal squamous cell carcinoma,hypoxia-inducible factor 1,polymorphism,vascular endothelial growth factor,microvascular density,recurrence
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