PT - JOURNAL ARTICLE AU - Carolina Cubillos-Zapata AU - Miguel Ángel Martínez-García AU - Elena Díaz-García AU - Sara García-Tovar AU - Francisco Campos-Rodríguez AU - Manuel Sánchez-de-la-Torre AU - Eduardo Nagore AU - Antonio Martorell-Calatayud AU - Luis Hernández Blasco AU - Esther Pastor AU - Jorge Abad-Capa AU - Josep María Montserrat AU - Valentín Cabriada-Nuño AU - Irene Cano-Pumarega AU - Jaime Corral-Peñafiel AU - Eva Arias AU - Olga Mediano AU - María Somoza-González AU - Joan Dalmau-Arias AU - Isaac Almendros AU - Ramón Farré AU - David Gozal AU - Francisco García-Río ED - , TI - Obstructive sleep apnoea is related to melanoma aggressiveness through paraspeckle protein-1 upregulation AID - 10.1183/13993003.00707-2022 DP - 2023 Feb 01 TA - European Respiratory Journal PG - 2200707 VI - 61 IP - 2 4099 - http://erj.ersjournals.com/content/61/2/2200707.short 4100 - http://erj.ersjournals.com/content/61/2/2200707.full SO - Eur Respir J2023 Feb 01; 61 AB - Background In patients with obstructive sleep apnoea (OSA), intermittent hypoxia induces overexpression of paraspeckle component (PSPC)1, a master modulator of transforming growth factor (TGF)-β signalling, which promotes cell cancer progression through epithelial–mesenchymal transition (EMT) and acquisition of cancer stem cell (CSC)-like features. However, the persistence of intermittent hypoxia-induced effects on PSPC1, and their consequences in cancer patients are not known. To this effect, circulating PSPC1 levels were compared in patients with cutaneous melanoma with or without OSA, and their relationship with tumour aggressiveness along with the in vitro effects of soluble PSPC1 and intermittent hypoxia on melanoma cell aggressiveness mechanisms were assessed.Methods In 292 cutaneous melanoma patients, sleep studies and serum levels of PSPC1 and TGF-β were evaluated. The effect of PSPC1 on expression of EMT and CSC transcription factors was assessed using melanoma cell lines with patient sera under both normoxia and intermittent hypoxia conditions.Results PSPC1 levels were higher in patients with moderate–severe OSA compared with mild OSA or non-OSA patients. Serum levels of PSPC1 were associated with several cutaneous melanoma clinical aggressiveness indicators. Both intermittent hypoxia exposures and serum from OSA patients upregulated TGF-β expression and amplified the expression of transcription factors associated with EMT activation and acquisition of CSC characteristics.Conclusion In cutaneous melanoma patients, OSA severity is associated with higher PSPC1 serum levels, which jointly with intermittent hypoxia would enhance the self-reprogramming capabilities of EMT and CSC feature acquisition of melanoma cells, promoting their intrinsic aggressiveness.In melanoma patients, sleep apnoea promotes the self-reprogramming capabilities of epithelial–mesenchymal transition and cancer stem cell-like features acquisition in tumour cells, increasing their intrinsic aggressiveness https://bit.ly/3eA2oxm