Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma
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 th...
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| creator | Cubillos-Zapata, Carolina Martínez-García, Miguel Ángel Díaz-García, Elena Jaureguizar, Ana Campos-Rodríguez, Francisco Sánchez-de-la-Torre, Manuel Nagore, Eduardo Martorell-Calatayud, Antonio Blasco, Luis Hernández Pastor, Esther Abad-Capa, Jorge Montserrat, Josep María Cabriada-Nuño, Valentín Cano-Pumarega, Irene Corral-Peñafiel, Jaime Arias, Eva Mediano, Olga Somoza-González, María Dalmau-Arias, Joan Almendros, Isaac Farré, Ramón López-Collazo, Eduardo Gozal, David García-Río, Francisco |
| description | 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. |
| doi_str_mv | 10.1038/s41598-020-72481-x |
| format | Article |
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-72481-x</identifier><identifier>PMID: 32968152</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67 ; 692/308 ; 692/4028 ; 692/420 ; 692/699 ; Adult ; Aged ; Cell Line, Tumor ; Female ; Humanities and Social Sciences ; Humans ; Leptin - blood ; Male ; Melanoma - blood ; Melanoma - complications ; Melanoma - pathology ; Melanoma, Cutaneous Malignant ; Middle Aged ; multidisciplinary ; Obesity - blood ; Obesity - complications ; Science ; Science (multidisciplinary) ; Skin Neoplasms - blood ; Skin Neoplasms - complications ; Skin Neoplasms - pathology ; Sleep Apnea, Obstructive - blood ; Sleep Apnea, Obstructive - complications ; Transforming Growth Factor beta1 - blood</subject><ispartof>Scientific reports, 2020-09, Vol.10 (1), p.15528-15528, Article 15528</ispartof><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361x-999c38c00fc2a1b3a9a1781abbf0e2b372413f6efc1159542affc3e6fdfcf0233</citedby><cites>FETCH-LOGICAL-c361x-999c38c00fc2a1b3a9a1781abbf0e2b372413f6efc1159542affc3e6fdfcf0233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511355/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511355/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32968152$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cubillos-Zapata, Carolina</creatorcontrib><creatorcontrib>Martínez-García, Miguel Ángel</creatorcontrib><creatorcontrib>Díaz-García, Elena</creatorcontrib><creatorcontrib>Jaureguizar, Ana</creatorcontrib><creatorcontrib>Campos-Rodríguez, Francisco</creatorcontrib><creatorcontrib>Sánchez-de-la-Torre, Manuel</creatorcontrib><creatorcontrib>Nagore, Eduardo</creatorcontrib><creatorcontrib>Martorell-Calatayud, Antonio</creatorcontrib><creatorcontrib>Blasco, Luis Hernández</creatorcontrib><creatorcontrib>Pastor, Esther</creatorcontrib><creatorcontrib>Abad-Capa, Jorge</creatorcontrib><creatorcontrib>Montserrat, Josep María</creatorcontrib><creatorcontrib>Cabriada-Nuño, Valentín</creatorcontrib><creatorcontrib>Cano-Pumarega, Irene</creatorcontrib><creatorcontrib>Corral-Peñafiel, Jaime</creatorcontrib><creatorcontrib>Arias, Eva</creatorcontrib><creatorcontrib>Mediano, Olga</creatorcontrib><creatorcontrib>Somoza-González, María</creatorcontrib><creatorcontrib>Dalmau-Arias, Joan</creatorcontrib><creatorcontrib>Almendros, Isaac</creatorcontrib><creatorcontrib>Farré, Ramón</creatorcontrib><creatorcontrib>López-Collazo, Eduardo</creatorcontrib><creatorcontrib>Gozal, David</creatorcontrib><creatorcontrib>García-Río, Francisco</creatorcontrib><title>Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>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.</description><subject>631/67</subject><subject>692/308</subject><subject>692/4028</subject><subject>692/420</subject><subject>692/699</subject><subject>Adult</subject><subject>Aged</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Leptin - blood</subject><subject>Male</subject><subject>Melanoma - blood</subject><subject>Melanoma - complications</subject><subject>Melanoma - pathology</subject><subject>Melanoma, Cutaneous Malignant</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Obesity - blood</subject><subject>Obesity - complications</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Skin Neoplasms - blood</subject><subject>Skin Neoplasms - complications</subject><subject>Skin Neoplasms - pathology</subject><subject>Sleep Apnea, Obstructive - blood</subject><subject>Sleep Apnea, Obstructive - complications</subject><subject>Transforming Growth Factor beta1 - blood</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kUtOHDEQhi2UKCDCBbJAXmbTwY_2THsTKUKBREJiQ9ZWtac8Y9Rtd2z3ZDgNh-FiOAwgsok3Zan--uvxEfKJsy-cye4st1zprmGCNUvRdrzZHZAjwVrVCCnEuzf_Q3KS8y2rTwndcv2BHEqhFx1X4ojsrnvMvtxRKAXDDAUzLRuk6BzaQqOjeUCcKEwBgcZAwRa_RXpzedE83HM64BaHTCGsaJnHmCis1wlzrppQA_WBTlA8hpLpH182dMQBQhzhI3nvYMh48hyPya-L7zfnP5qr68uf59-uGisXfNdora3sLGPOCuC9BA182XHoe8dQ9LLuzqVboLO83kO1ApyzEhdu5axjQspj8nXvO839iCtbJ0kwmCn5EdKdieDNv5ngN2Ydt2apOJdKVYPPzwYp_p4xFzP6bHGoa2CcsxFtq_RS8iep2EttijkndK9tODN_qZk9NVOpmSdqZleLTt8O-FrywqgK5F6QayqsMZnbOKdQj_Y_20dstqch</recordid><startdate>20200923</startdate><enddate>20200923</enddate><creator>Cubillos-Zapata, Carolina</creator><creator>Martínez-García, Miguel Ángel</creator><creator>Díaz-García, Elena</creator><creator>Jaureguizar, Ana</creator><creator>Campos-Rodríguez, Francisco</creator><creator>Sánchez-de-la-Torre, Manuel</creator><creator>Nagore, Eduardo</creator><creator>Martorell-Calatayud, Antonio</creator><creator>Blasco, Luis Hernández</creator><creator>Pastor, Esther</creator><creator>Abad-Capa, Jorge</creator><creator>Montserrat, Josep María</creator><creator>Cabriada-Nuño, Valentín</creator><creator>Cano-Pumarega, Irene</creator><creator>Corral-Peñafiel, Jaime</creator><creator>Arias, Eva</creator><creator>Mediano, Olga</creator><creator>Somoza-González, María</creator><creator>Dalmau-Arias, Joan</creator><creator>Almendros, Isaac</creator><creator>Farré, Ramón</creator><creator>López-Collazo, Eduardo</creator><creator>Gozal, David</creator><creator>García-Río, Francisco</creator><general>Nature Publishing Group UK</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200923</creationdate><title>Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma</title><author>Cubillos-Zapata, Carolina ; Martínez-García, Miguel Ángel ; Díaz-García, Elena ; Jaureguizar, Ana ; Campos-Rodríguez, Francisco ; Sánchez-de-la-Torre, Manuel ; Nagore, Eduardo ; Martorell-Calatayud, Antonio ; Blasco, Luis Hernández ; Pastor, Esther ; Abad-Capa, Jorge ; Montserrat, Josep María ; Cabriada-Nuño, Valentín ; Cano-Pumarega, Irene ; Corral-Peñafiel, Jaime ; Arias, Eva ; Mediano, Olga ; Somoza-González, María ; Dalmau-Arias, Joan ; Almendros, Isaac ; Farré, Ramón ; López-Collazo, Eduardo ; Gozal, David ; García-Río, Francisco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361x-999c38c00fc2a1b3a9a1781abbf0e2b372413f6efc1159542affc3e6fdfcf0233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>631/67</topic><topic>692/308</topic><topic>692/4028</topic><topic>692/420</topic><topic>692/699</topic><topic>Adult</topic><topic>Aged</topic><topic>Cell Line, Tumor</topic><topic>Female</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Leptin - blood</topic><topic>Male</topic><topic>Melanoma - blood</topic><topic>Melanoma - complications</topic><topic>Melanoma - pathology</topic><topic>Melanoma, Cutaneous Malignant</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>Obesity - blood</topic><topic>Obesity - complications</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Skin Neoplasms - blood</topic><topic>Skin Neoplasms - complications</topic><topic>Skin Neoplasms - pathology</topic><topic>Sleep Apnea, Obstructive - blood</topic><topic>Sleep Apnea, Obstructive - complications</topic><topic>Transforming Growth Factor beta1 - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cubillos-Zapata, Carolina</creatorcontrib><creatorcontrib>Martínez-García, Miguel Ángel</creatorcontrib><creatorcontrib>Díaz-García, Elena</creatorcontrib><creatorcontrib>Jaureguizar, Ana</creatorcontrib><creatorcontrib>Campos-Rodríguez, Francisco</creatorcontrib><creatorcontrib>Sánchez-de-la-Torre, Manuel</creatorcontrib><creatorcontrib>Nagore, Eduardo</creatorcontrib><creatorcontrib>Martorell-Calatayud, Antonio</creatorcontrib><creatorcontrib>Blasco, Luis Hernández</creatorcontrib><creatorcontrib>Pastor, Esther</creatorcontrib><creatorcontrib>Abad-Capa, Jorge</creatorcontrib><creatorcontrib>Montserrat, Josep María</creatorcontrib><creatorcontrib>Cabriada-Nuño, Valentín</creatorcontrib><creatorcontrib>Cano-Pumarega, Irene</creatorcontrib><creatorcontrib>Corral-Peñafiel, Jaime</creatorcontrib><creatorcontrib>Arias, Eva</creatorcontrib><creatorcontrib>Mediano, Olga</creatorcontrib><creatorcontrib>Somoza-González, María</creatorcontrib><creatorcontrib>Dalmau-Arias, Joan</creatorcontrib><creatorcontrib>Almendros, Isaac</creatorcontrib><creatorcontrib>Farré, Ramón</creatorcontrib><creatorcontrib>López-Collazo, Eduardo</creatorcontrib><creatorcontrib>Gozal, David</creatorcontrib><creatorcontrib>García-Río, Francisco</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cubillos-Zapata, Carolina</au><au>Martínez-García, Miguel Ángel</au><au>Díaz-García, Elena</au><au>Jaureguizar, Ana</au><au>Campos-Rodríguez, Francisco</au><au>Sánchez-de-la-Torre, Manuel</au><au>Nagore, Eduardo</au><au>Martorell-Calatayud, Antonio</au><au>Blasco, Luis Hernández</au><au>Pastor, Esther</au><au>Abad-Capa, Jorge</au><au>Montserrat, Josep María</au><au>Cabriada-Nuño, Valentín</au><au>Cano-Pumarega, Irene</au><au>Corral-Peñafiel, Jaime</au><au>Arias, Eva</au><au>Mediano, Olga</au><au>Somoza-González, María</au><au>Dalmau-Arias, Joan</au><au>Almendros, Isaac</au><au>Farré, Ramón</au><au>López-Collazo, Eduardo</au><au>Gozal, David</au><au>García-Río, Francisco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-09-23</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>15528</spage><epage>15528</epage><pages>15528-15528</pages><artnum>15528</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32968152</pmid><doi>10.1038/s41598-020-72481-x</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67 692/308 692/4028 692/420 692/699 Adult Aged Cell Line, Tumor Female Humanities and Social Sciences Humans Leptin - blood Male Melanoma - blood Melanoma - complications Melanoma - pathology Melanoma, Cutaneous Malignant Middle Aged multidisciplinary Obesity - blood Obesity - complications Science Science (multidisciplinary) Skin Neoplasms - blood Skin Neoplasms - complications Skin Neoplasms - pathology Sleep Apnea, Obstructive - blood Sleep Apnea, Obstructive - complications Transforming Growth Factor beta1 - blood |
| title | Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma |
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