HIF-1alpha Expression Profile in Intratumoral and Peritumoral Inflammatory Cells as a Prognostic Marker for Squamous Cell Carcinoma of the Oral Cavity

Author(s):Show less -

Mendes, Suzanny Oliveira ^[1] ; dos Santos, Marcelo ^{[1, 2]} ; Peterle, Gabriela Tonini ^[1] ; Maia, Lucas de Lima ^[1] ; Stur, Elaine ^[1] ; Agostini, Lidiane Pignaton ^[1] ; de Carvalho, Marcos Brasilino ^[3] ; Tajara, Eloiza Helena ^[4] ; Louro, Iuri Drumond ^[1] ; Trivilin, Leonardo Oliveira ^[1] ; Alvares da Silva-Conforti, Adriana Madeira ^[1]

Affiliation

^[1] Univ Fed Espirito Santo, Programa Pos Grad Biotecnol Renorbio, Vitoria, ES - Brazil

^[2] Univ Fed Rio Grande do Norte, Dept Med, Caico, RN - Brazil

^[3] Hosp Heliopolis, Lab Biol Mol, Sao Paulo - Brazil

^[4] Fac Med Sao Jose do Rio Preto, Dept Biol Mol, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS One; v. 9, n. 1 JAN 9 2014.
• Web of Science Citations: 7

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. (AU)

• FAPESP's process: 04/12054-9 - Markers of aggressive behavior in head and neck tumors
• Grantee: Eloiza Helena Tajara da Silva
• Support Opportunities: Research Projects - Thematic Grants