TY - JOUR
T1 - Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma
AU - Cubillos-Zapata, Carolina
AU - Martínez-García, Miguel Ángel
AU - Díaz-García, Elena
AU - Jaureguizar, Ana
AU - Campos-Rodríguez, Francisco
AU - Sánchez-de-la-Torre, Manuel
AU - Nagore, Eduardo
AU - Martorell-Calatayud, Antonio
AU - Blasco, Luis Hernández
AU - Pastor, Esther
AU - Abad Capa, Jorge
AU - Montserrat, Josep María
AU - Cabriada-Nuño, Valentín
AU - Cano-Pumarega, Irene
AU - Corral-Peñafiel, Jaime
AU - Arias, Eva
AU - Mediano, Olga
AU - Somoza-González, María
AU - Dalmau-Arias, Joan
AU - Almendros, Isaac
AU - Farré, Ramon
AU - López-Collazo, Eduardo
AU - Gozal, David
AU - García-Rio, Francisco
PY - 2020
Y1 - 2020
N2 - Active 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.
AB - Active 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.
KW - Cancer
KW - Diseases
KW - Medical research
KW - Oncology
KW - Pathogenesis
U2 - 10.1038/s41598-020-72481-x
DO - 10.1038/s41598-020-72481-x
M3 - Article
C2 - 32968152
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
ER -
