Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1α but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients
Isaac Almendros, Miguel Ángel Martínez-García, Francisco Campos-Rodríguez, Erica Riveiro-Falkenbach, José L. Rodríguez-Peralto, Eduardo Nagore, Antonio Martorell-Calatayud, Luis Hernández Blasco, Jose Bañuls Roca, Eusebi Chiner Vives, Alicia Sánchez-de-la-Torre, Jorge Abad-Capa, Josep Maria Montserrat, Amalia Pérez-Gil, Valentín Cabriada-Nuño, Irene Cano-Pumarega, Jaime Corral-Peñafiel, Trinidad Diaz-Cambriles, Olga Mediano, Joan Dalmau-Arias, Ramon Farré, David Gozal, On Behalf of the Spanish Sleep Network, Elidia Molina Herrera, Rosa M. García Martín, Maria Niveiro de Jaime, Sara Moreno, Ferran Barbé Ilia, Manuel Sánchez de la Torre, Esther de Eusebio, Pedro Landete, Manuel Moragón Gordon, Eva Arias, Fernando Masa, Carlos González Herrada, Cristina Carrera, Aida Muñoz Ferrer, Aram Boada, Ana Fortuna, Mercé Mayos, Jesús Gardeazabal García
Abstract
Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions via intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea-hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, <25, 25-50, 51-75, >75%) was blindly tabulated for VEGF expression, and as 0, 0-5.9, 6.0-10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those <6%, and VEGF expression >75% of cells was compared with those with <75%. 376 patients were included. High expression of VEGF and HIF-1α were seen in 88.8 and 4.2% of samples, respectively. High expression of VEGF was only associated with increasing age. However, high expression of HIF-1α was significantly associated with age, Breslow index, AHI, and DI4%. Logistic regression showed that DI4% [OR 1.03 (95% CI: 1.01-1.06)] and Breslow index [OR 1.28 (95% CI: 1.18-1.46)], but not AHI, remained independently associated with the presence of high HIF-1α expression. Thus, IH emerges as an independent risk factor for higher HIF-1α expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 May 2018.
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