Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients

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)-1 alpha and vascular endothelial growth factor (VE...

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Autores: Almendros, Isaac, Angel Martinez-Garcia, Miguel, Campos-Rodriguez, Francisco, Riveiro-Falkenbach, Erica, Rodriguez-Peralto, Jose L., Nagore, Eduardo, Martorell-Calatayud, Antonio, HERNÁNDEZ, L., BAÑULS, J., Chiner Vives, Eusebi, Sanchez-de-la-Torre, Alicia, Abad-Capa, Jorge, Maria Montserrat, Josep, Perez-Gil, Amalia, Cabriada-Nuno, Valentin, Cano-Pumarega, Irene, Corral-Penafiel, Jaime, Diaz-Cambriles, Trinidad, Mediano, Olga, Dalmau-Arias, Joan, Farre, Ramon, Gozal, David, Spanish Sleep Network
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p2891
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/2891
Access Level:acceso abierto
Palabra clave:melanoma
intermittent hypoxia
obstructive sleep apnea
hypoxia-inducible factor
vascular endothelial growth factor
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spelling Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma PatientsAlmendros, IsaacAngel Martinez-Garcia, MiguelCampos-Rodriguez, FranciscoRiveiro-Falkenbach, EricaRodriguez-Peralto, Jose L.Nagore, EduardoMartorell-Calatayud, AntonioHERNÁNDEZ, L.BAÑULS, J.Chiner Vives, EusebiSanchez-de-la-Torre, AliciaAbad-Capa, JorgeMaria Montserrat, JosepPerez-Gil, AmaliaCabriada-Nuno, ValentinCano-Pumarega, IreneCorral-Penafiel, JaimeDiaz-Cambriles, TrinidadMediano, OlgaDalmau-Arias, JoanFarre, RamonGozal, DavidSpanish Sleep Networkmelanomaintermittent hypoxiaobstructive sleep apneahypoxia-inducible factorvascular endothelial growth factorEpidemiological 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)-1 alpha 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-1 alpha 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-1 alpha 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-1 alpha expression, respectively. Cases with HIF-1 alpha 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-1 alpha 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-1 alpha 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-1 alpha expression. Thus, IH emerges as an independent risk factor for higher HIF-1 alpha expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.FRONTIERS MEDIA SA2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/2891Frontiers in NeurologyISSN: 16642295reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p28912026-06-11T12:45:17Z
dc.title.none.fl_str_mv Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients
title Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients
spellingShingle Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients
Almendros, Isaac
melanoma
intermittent hypoxia
obstructive sleep apnea
hypoxia-inducible factor
vascular endothelial growth factor
title_short Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients
title_full Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients
title_fullStr Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients
title_full_unstemmed Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients
title_sort Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1 alpha but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients
dc.creator.none.fl_str_mv Almendros, Isaac
Angel Martinez-Garcia, Miguel
Campos-Rodriguez, Francisco
Riveiro-Falkenbach, Erica
Rodriguez-Peralto, Jose L.
Nagore, Eduardo
Martorell-Calatayud, Antonio
HERNÁNDEZ, L.
BAÑULS, J.
Chiner Vives, Eusebi
Sanchez-de-la-Torre, Alicia
Abad-Capa, Jorge
Maria Montserrat, Josep
Perez-Gil, Amalia
Cabriada-Nuno, Valentin
Cano-Pumarega, Irene
Corral-Penafiel, Jaime
Diaz-Cambriles, Trinidad
Mediano, Olga
Dalmau-Arias, Joan
Farre, Ramon
Gozal, David
Spanish Sleep Network
author Almendros, Isaac
author_facet Almendros, Isaac
Angel Martinez-Garcia, Miguel
Campos-Rodriguez, Francisco
Riveiro-Falkenbach, Erica
Rodriguez-Peralto, Jose L.
Nagore, Eduardo
Martorell-Calatayud, Antonio
HERNÁNDEZ, L.
BAÑULS, J.
Chiner Vives, Eusebi
Sanchez-de-la-Torre, Alicia
Abad-Capa, Jorge
Maria Montserrat, Josep
Perez-Gil, Amalia
Cabriada-Nuno, Valentin
Cano-Pumarega, Irene
Corral-Penafiel, Jaime
Diaz-Cambriles, Trinidad
Mediano, Olga
Dalmau-Arias, Joan
Farre, Ramon
Gozal, David
Spanish Sleep Network
author_role author
author2 Angel Martinez-Garcia, Miguel
Campos-Rodriguez, Francisco
Riveiro-Falkenbach, Erica
Rodriguez-Peralto, Jose L.
Nagore, Eduardo
Martorell-Calatayud, Antonio
HERNÁNDEZ, L.
BAÑULS, J.
Chiner Vives, Eusebi
Sanchez-de-la-Torre, Alicia
Abad-Capa, Jorge
Maria Montserrat, Josep
Perez-Gil, Amalia
Cabriada-Nuno, Valentin
Cano-Pumarega, Irene
Corral-Penafiel, Jaime
Diaz-Cambriles, Trinidad
Mediano, Olga
Dalmau-Arias, Joan
Farre, Ramon
Gozal, David
Spanish Sleep Network
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv melanoma
intermittent hypoxia
obstructive sleep apnea
hypoxia-inducible factor
vascular endothelial growth factor
topic melanoma
intermittent hypoxia
obstructive sleep apnea
hypoxia-inducible factor
vascular endothelial growth factor
description 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)-1 alpha 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-1 alpha 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-1 alpha 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-1 alpha expression, respectively. Cases with HIF-1 alpha 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-1 alpha 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-1 alpha 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-1 alpha expression. Thus, IH emerges as an independent risk factor for higher HIF-1 alpha expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/2891
url https://fisabio.portalinvestigacion.com/publicaciones/2891
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv FRONTIERS MEDIA SA
publisher.none.fl_str_mv FRONTIERS MEDIA SA
dc.source.none.fl_str_mv Frontiers in Neurology
ISSN: 16642295
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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