AUTHOR=Almendros Isaac , Martínez-García Miguel Ángel , Campos-Rodríguez Francisco , Riveiro-Falkenbach Erica , Rodríguez-Peralto José L. , Nagore Eduardo , Martorell-Calatayud Antonio , Hernández Blasco Luis , Bañuls Roca Jose , Chiner Vives Eusebi , Sánchez-de-la-Torre Alicia , Abad-Capa Jorge , Montserrat Josep Maria , Pérez-Gil Amalia , Cabriada-Nuño Valentín , Cano-Pumarega Irene , Corral-Peñafiel Jaime , Diaz-Cambriles Trinidad , Mediano Olga , Dalmau-Arias Joan , Farré Ramon , Gozal David ,  On Behalf of the Spanish Sleep Network , Herrera Elidia Molina , Martín Rosa M. García , de Jaime Maria Niveiro , Moreno Sara , Ilia Ferran Barbé , de la Torre Manuel Sánchez , de Eusebio Esther , Landete Pedro , Gordon Manuel Moragón , Arias Eva , Masa Fernando , Herrada Carlos González , Carrera Cristina , Ferrer Aida Muñoz , Boada Aram , Fortuna Ana , Mayos Mercé , García Jesús Gardeazabal 

TITLE=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

JOURNAL=Frontiers in Neurology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.00272

DOI=10.3389/fneur.2018.00272

ISSN=1664-2295

ABSTRACT=Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain these associations have included enhanced HIF-1α and 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.