HIF-1alpha expression profile in intratumoral and peritumoral inflammatory cells as a prognostic marker for squamous cell carcinoma of the oral cavity

• Published in: PloS one Vol. 9; no. 1; p. e84923
• Main Authors: Mendes, Suzanny Oliveira, dos Santos, Marcelo, Peterle, Gabriela Tonini, Maia, Lucas de Lima, Stur, Elaine, Agostini, Lidiane Pignaton, de Carvalho, Marcos Brasilino, Tajara, Eloiza Helena, Louro, Iúri Drumond, Trivilin, Leonardo Oliveira, da Silva-Conforti, Adriana Madeira Álvares
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09-01-2014; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Antigens; Biology; Biomarkers, Tumor - metabolism; Breast cancer; Cancer therapies; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Female; Gene Expression Regulation, Neoplastic; Genetic aspects; Head & neck cancer; Health risks; Humans; Hypoxia; Hypoxia-inducible factor 1; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor 1a; Immunosuppression; Immunotherapy; Inflammation; Inflammation - pathology; Lymphocytes; Lymphocytes - metabolism; Lymphoid cells; Male; Medical prognosis; Medicine; Metastasis; Middle Aged; Mortality; Mouth Neoplasms - diagnosis; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Oral cancer; Oral cavity; Prognosis; Risk assessment; Risk factors; Rodents; Squamous cell carcinoma; Studies; Surgery; Tumor markers; Tumor Microenvironment; Tumors; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084923

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.