Cubillos-Zapata, CarolinaMartínez-García, Miguel ÁngelDíaz-García, ElenaJaureguizar, AnaCampos-Rodríguez, FranciscoSánchez-de-la-Torre, ManuelNagore, EduardoMartorell-Calatayud, AntonioHernández Blasco, LuisPastor, EstherAbad-Capa, JorgeMontserrat, Josep MaríaCabriada-Nuño, ValentínCano-Pumarega, IreneCorral-Peñafiel, JaimeArias, EvaMediano, OlgaSomoza-González, MaríaDalmau-Arias, JoanAlmendros, IsaacFarré, RamónLópez-Collazo, EduardoGozal, DavidGarcía-Río, Francisco2022-10-312022-10-312020-09-23Cubillos-Zapata C, Martínez-García MÁ, Díaz-García E, Jaureguizar A, Campos-Rodríguez F, Sánchez-de-la-Torre M, et al. Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma. Sci Rep. 2020 Sep 23;10(1):15528http://hdl.handle.net/10668/4309Active transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/TGF‑ß1Transforming growth factor beta1Skin neoplasmsTumorObesityApneaLeptinSleepFactor de crecimiento transformador beta1Neoplasias cutáneasObesidadLeptinaSueñoMedical Subject Headings::Persons::Persons::Age Groups::AdultMedical Subject Headings::Persons::Persons::Age Groups::Adult::AgedMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, TumorMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Adipokines::LeptinMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::MelanomaMedical Subject Headings::Persons::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::ObesityMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Skin NeoplasmsMedical Subject Headings::Diseases::Respiratory Tract Diseases::Respiration Disorders::Apnea::Sleep Apnea Syndromes::Sleep Apnea, ObstructiveMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Transforming Growth Factor beta::Transforming Growth Factor beta1Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cytogenetic Analysis::Mitotic IndexMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::CytokinesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::PrognosisMedical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Psychophysiology::Sleepresearch article32968152open access10.1038/s41598-020-72481-x2045-2322PMC7511355