title: A high HIF-1α expression genotype is associated with poor prognosis of upper aerodigestive tract carcinoma patients.
abstract: The aim of the present study was to evaluate the role of HIF-1α genetic polymorphisms and protein expression in the development of metastasis in upper aerodigestive tract cancer (UADTC) patients. The expression of pro-angiogenic markers was also evaluated. Protein expression was analysed using immunohistochemistry, and RFLP analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 52 patients with UADTC. Primary lesions were divided into 2 groups according to the absence or presence of metastasis. Lymph node samples were divided into 3 groups: metastatic lymph nodes, non-metastatic lymph nodes (both derived from patients with metastatic disease), and control lymph nodes, which were obtained from patients without any metastasis. The allele T was more frequently found in patients with metastatic disease. HIF-1α protein expression in the lymph nodes was increased in the presence of the T allele. Metastatic lymph nodes showed lower levels of HIF-1α, VEGFR1, and MMP-9 proteins compared to lymph nodes without metastasis, while VEGFR2 protein levels were increased. In agreement, HIF-1α expression was correlated with MMP-9. Cox regression analysis demonstrated that higher HIF-1α and MMP-9 protein expression levels and GA and GG genotypes were associated with poor survival. Our findings show that the C1772T and G1790A polymorphisms of the HIF-1α gene are associated with increased expression of the HIF-1α protein in UADTC. The present data indicate that non-metastatic tissues express higher levels of HIF-1α, VEGFR1, and MMP-9, while in metastatic lymph nodes, VEGFR2 protein expression is elevated. The present study also shows that the HIF-1α G1790A polymorphism and its protein expression have an impact on the prognosis of UADTC patients.
authors.affiliation: Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Brazil.
authors.forename: Carlos Alberto de Carvalho
authors.initials: CA
authors.lastname: Fraga
authors.forename: Marcos Vinícius Macedo
authors.initials: MV
authors.lastname: de Oliveira
authors.forename: Érica Silva
authors.initials: ÉS
authors.lastname: de Oliveira
authors.forename: Lucas Oliveira
authors.initials: LO
authors.lastname: Barros
authors.forename: Francis Balduino Guimarães
authors.initials: FB
authors.lastname: Santos
authors.forename: Ricardo Santiago
authors.initials: RS
authors.lastname: Gomez
authors.forename: Alfredo Maurício Batista
authors.initials: AM
authors.lastname: De-Paula
authors.forename: André Luiz Sena
authors.initials: AL
authors.lastname: Guimarães
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000071063:Endoglin; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010039:Otorhinolaryngologic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D020780:Matrix Metalloproteinase 9