title: HIF-1alpha expression profile in intratumoral and peritumoral inflammatory cells as a prognostic marker for squamous cell carcinoma of the oral cavity.
abstract: The HIF-1 transcriptional complex is responsible for controlling transcription of over 100 genes involved in cell hypoxia response. HIF-1alpha subunit is stabilized in hypoxia conditions, creating the HIF-1 nuclear transcription factor. In inflammatory cells, high HIF-1alpha expression induces lymphocytic immunosuppression, decreasing tumoral antigen recognition, which promotes tumor growth. The present work investigated the relationship between HIF-1alpha expression in lymphocytes populating the intratumoral and peritumoral region of 56 patients with oral cancer. Our data indicates a prognostic value for this expression. High HIF-1alpha expression in peritumoral inflammatory cells is significantly related to worse patient outcome, whereas high expression in the intratumoral lymphoid cells correlates with a better prognosis. A risk profile indicating the chance of disease relapse and death was designed based on HIF-1alpha expression in tumoral inflammatory cells, defining low, intermediate and high risks. This risk profile was able to determine that high HIF-1alpha expression in peritumoral cells correlates with worse prognosis, independently of intratumoral expression. Low HIF-1alpha in tumor margins and high expression in the tumor was considered a low risk profile, showing no cases of disease relapse and disease related death. Intermediate risk was associated with low expression in tumor and tumor margins. Our results suggest that HIF-1alpha expression in tumor and peritumoral inflammatory cells may play an important role as prognostic tumor marker.
authors.affiliation: Programa de Pós Graduação em Biotecnologia - Renorbio, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Suzanny Oliveira
authors.initials: SO
authors.lastname: Mendes
authors.affiliation: Programa de Pós Graduação em Biotecnologia - Renorbio, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil ; Departamento de Medicina, Universidade Federal do Rio Grande do Norte, Caicó, RN, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: dos Santos
authors.affiliation: Programa de Pós Graduação em Biotecnologia - Renorbio, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Gabriela Tonini
authors.initials: GT
authors.lastname: Peterle
authors.affiliation: Programa de Pós Graduação em Biotecnologia - Renorbio, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Lucas de Lima
authors.initials: Lde L
authors.lastname: Maia
authors.affiliation: Programa de Pós Graduação em Biotecnologia - Renorbio, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: Stur
authors.affiliation: Programa de Pós Graduação em Biotecnologia - Renorbio, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Lidiane Pignaton
authors.initials: LP
authors.lastname: Agostini
authors.affiliation: Laboratório de Biologia Molecular, Hospital Heliópolis, São Paulo, São Paulo, Brazil.
authors.forename: Marcos Brasilino
authors.initials: MB
authors.lastname: de Carvalho
authors.affiliation: Departamento de Biologia Molecular, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, São Paulo, Brazil.
authors.forename: Eloiza Helena
authors.initials: EH
authors.lastname: Tajara
authors.affiliation: Programa de Pós Graduação em Biotecnologia - Renorbio, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Iúri Drumond
authors.initials: ID
authors.lastname: Louro
authors.affiliation: Programa de Pós Graduação em Biotecnologia - Renorbio, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Leonardo Oliveira
authors.initials: LO
authors.lastname: Trivilin
authors.affiliation: Programa de Pós Graduação em Biotecnologia - Renorbio, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil.
authors.forename: Adriana Madeira Álvares
authors.initials: AM
authors.lastname: da Silva-Conforti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit