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
Por:
Almendros, I, Angel Martinez-Garcia, M, Campos-Rodriguez, F, Riveiro-Falkenbach, E, Rodriguez-Peralto, J, Nagore, E, Martorell-Calatayud, A, Hernández L, Bañuls J, Chiner Vives, E, Sanchez-de-la-Torre, A, Abad-Capa, J, Maria Montserrat, J, Perez-Gil, A, Cabriada-Nuno, V, Cano-Pumarega, I, Corral-Penafiel, J, Diaz-Cambriles, T, Mediano, O, Dalmau-Arias, J, Farre, R, Gozal, D and Spanish Sleep Network
Publicada:
26 abr 2018
Resumen:
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.
Filiaciones:
Almendros, I:
Univ Barcelona, Fac Med & Ciencies Salut, Unitat Biofis & Bioengn, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Inst Invest Biomed August Pi i Sunyer IDIBAPS, Barcelona, Spain
Angel Martinez-Garcia, M:
Hosp Univ & Politecn Fe, Resp Dept, Valencia, Spain
Campos-Rodriguez, F:
Hosp Univ Valme, Resp Dept, Seville, Spain
Riveiro-Falkenbach, E:
Univ Complutense, Hosp Univ Octubre CIBERONC 12, Med Sch, Inst i 12,Pathol Dept, Madrid, Spain
Rodriguez-Peralto, J:
Univ Complutense, Hosp Univ Octubre CIBERONC 12, Med Sch, Inst i 12,Pathol Dept, Madrid, Spain
Nagore, E:
Inst Valenciano Oncol, Dermatol Dept, Valencia, Spain
Martorell-Calatayud, A:
Hosp Manises, Dermatol Dept, Valencia, Spain
Hernández L:
Univ Alicante, Hosp Gral, ISABIAL, Resp Dept, Alicante, Spain
Univ Miguel Hernandez, Dept Med Clin, Elche, Spain
Bañuls J:
Univ Alicante, Hosp Gral, ISABIAL, Resp Dept, Alicante, Spain
Univ Miguel Hernandez, Dept Med Clin, Elche, Spain
:
Hosp San Juan Alicante, Resp Dept, Alicante, Spain
Sanchez-de-la-Torre, A:
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ Arnau Vilanova & Santa Maria, IRBLleida, Grp Translat Res Resp Med, Resp Dept, Lleida, Spain
Abad-Capa, J:
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Hosp Badalona Germans Trias & Pujol, Ctr Invest Biomed, Resp Dept, Madrid, Spain
Maria Montserrat, J:
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Hosp Clin IDIBAPS, Resp Dept, Barcelona, Spain
Perez-Gil, A:
Hosp Valme, Dermatol Dept, Seville, Spain
Cabriada-Nuno, V:
Hosp Univ Cruces, Resp Dept, Bilbao, Spain
Cano-Pumarega, I:
Hosp Univ Getafe, Resp Dept, Madrid, Spain
Corral-Penafiel, J:
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ S Pedro Alcantara, Resp Dept, Caceres, Spain
Diaz-Cambriles, T:
Hosp 12 Octubre, Resp Dept, Madrid, Spain
Mediano, O:
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Hosp Univ Guadalajara, CIBER Enfermedades Resp, Resp Dept, Madrid, Spain
Dalmau-Arias, J:
Hosp Santa Creu & Sant Pau, Dermatol Dept, Barcelona, Spain
Farre, R:
Univ Barcelona, Fac Med & Ciencies Salut, Unitat Biofis & Bioengn, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
Inst Invest Biomed August Pi i Sunyer IDIBAPS, Barcelona, Spain
Gozal, D:
Univ Chicago, Pritzker Sch Med, Dept Pediat, Biol Sci Div, Chicago, IL 60637 USA
gold, Green Published
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