{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:40:24Z","timestamp":1778218824960,"version":"3.51.4"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T00:00:00Z","timestamp":1576800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["BFU2014-58429-P"],"award-info":[{"award-number":["BFU2014-58429-P"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["BFU2017-88692-P"],"award-info":[{"award-number":["BFU2017-88692-P"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011596","name":"Conselleria d'Educaci\u00f3, Investigaci\u00f3, Cultura i Esport","doi-asserted-by":"publisher","award":["GVPROMETEO2016-123"],"award-info":[{"award-number":["GVPROMETEO2016-123"]}],"id":[{"id":"10.13039\/501100011596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0223341","type":"journal-article","created":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T13:29:36Z","timestamp":1576848576000},"page":"e0223341","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma"],"prefix":"10.1371","volume":"14","author":[{"given":"David","family":"Herv\u00e1s-Mar\u00edn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faatiemah","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Onofre","family":"Sanmart\u00edn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7369-8388","authenticated-orcid":true,"given":"Jose Antonio","family":"L\u00f3pez-Guerrero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Carmen","family":"Ba\u00f1\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6910-5845","authenticated-orcid":true,"given":"J. Carlos","family":"Igual","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inma","family":"Quilis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Sandoval","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2019,12,20]]},"reference":[{"issue":"1","key":"pone.0223341.ref001","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.sder.2011.01.002","article-title":"No en d in sight: the skin cancer epidemic continues","volume":"30","author":"MR Donaldson","year":"2011","journal-title":"Semin Cutan Med Surg"},{"issue":"13","key":"pone.0223341.ref002","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1056\/NEJM200103293441306","article-title":"Cutaneous squamous-cell carcinoma","volume":"344","author":"M Alam","year":"2001","journal-title":"N Engl J Med"},{"issue":"2","key":"pone.0223341.ref003","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/bjd.15324","article-title":"Cutaneous squamous cell carcinoma: an epidemiological review","volume":"177","author":"AC Green","year":"2017","journal-title":"Br J Dermatol"},{"issue":"9","key":"pone.0223341.ref004","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/j.jid.2017.04.020","article-title":"Incidence, Mortality, and Trends of Nonmelanoma Skin Cancer in Germany","volume":"137","author":"U Leiter","year":"2017","journal-title":"J Invest Dermatol"},{"issue":"5","key":"pone.0223341.ref005","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1001\/jamadermatol.2013.2139","article-title":"Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study","volume":"149","author":"CD Schmults","year":"2013","journal-title":"JAMA Dermatol"},{"key":"pone.0223341.ref006","article-title":"Performance of the American Joint Committee on Cancer Staging Manual, 8th Edition vs the Brigham and Women's Hospital Tumor Classification System for Cutaneous Squamous Cell Carcinoma","author":"ES Ruiz","year":"2019","journal-title":"JAMA Dermatol"},{"issue":"1","key":"pone.0223341.ref007","doi-asserted-by":"crossref","first-page":"3667","DOI":"10.1038\/s41467-018-06027-1","article-title":"The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature","volume":"9","author":"GJ Inman","year":"2018","journal-title":"Nat Commun"},{"issue":"24","key":"pone.0223341.ref008","doi-asserted-by":"crossref","first-page":"6582","DOI":"10.1158\/1078-0432.CCR-14-1768","article-title":"Mutational landscape of aggressive cutaneous squamous cell carcinoma","volume":"20","author":"CR Pickering","year":"2014","journal-title":"Clin Cancer Res"},{"issue":"10","key":"pone.0223341.ref009","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1038\/jid.2014.154","article-title":"NOTCH1 mutations occur early during cutaneous squamous cell carcinogenesis","volume":"134","author":"AP South","year":"2014","journal-title":"J Invest Dermatol"},{"issue":"1","key":"pone.0223341.ref010","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2340\/00015555-2181","article-title":"The Promise of Genomics and the Development of Targeted Therapies for Cutaneous Squamous Cell Carcinoma","volume":"96","author":"CA Harwood","year":"2016","journal-title":"Acta Derm Venereol"},{"issue":"2","key":"pone.0223341.ref011","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1158\/2159-8290.CD-11-0028","article-title":"Temporal dissection of tumorigenesis in primary cancers","volume":"1","author":"S Durinck","year":"2011","journal-title":"Cancer Discov"},{"issue":"3","key":"pone.0223341.ref012","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/humu.10179","article-title":"TP53 mutations in human skin cancers","volume":"21","author":"G Giglia-Mari","year":"2003","journal-title":"Hum Mutat"},{"issue":"43","key":"pone.0223341.ref013","doi-asserted-by":"crossref","first-page":"17761","DOI":"10.1073\/pnas.1114669108","article-title":"Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma","volume":"108","author":"NJ Wang","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0223341.ref014","doi-asserted-by":"crossref","first-page":"12493","DOI":"10.1038\/ncomms12493","article-title":"Inactivation of TGFbeta receptors in stem cells drives cutaneous squamous cell carcinoma","volume":"7","author":"P Cammareri","year":"2016","journal-title":"Nat Commun"},{"issue":"2","key":"pone.0223341.ref015","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/bjc.2013.760","article-title":"Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling","volume":"110","author":"SR Lambert","year":"2014","journal-title":"Br J Cancer"},{"issue":"5","key":"pone.0223341.ref016","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/j.juro.2012.07.003","article-title":"MYC copy number gains are associated with poor outcome in penile squamous cell carcinoma","volume":"188","author":"E Masferrer","year":"2012","journal-title":"J Urol"},{"issue":"3","key":"pone.0223341.ref017","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1056\/NEJMoa1105358","article-title":"RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors","volume":"366","author":"F Su","year":"2012","journal-title":"N Engl J Med"},{"issue":"2","key":"pone.0223341.ref018","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1600-0625.2009.01028.x","article-title":"Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas","volume":"19","author":"A Toll","year":"2010","journal-title":"Exp Dermatol"},{"issue":"5","key":"pone.0223341.ref019","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/mc.20716","article-title":"Fyn is induced by Ras\/PI3K\/Akt signaling and is required for enhanced invasion\/migration","volume":"50","author":"V Yadav","year":"2011","journal-title":"Mol Carcinog"},{"issue":"10","key":"pone.0223341.ref020","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1158\/1940-6207.CAPR-10-0058","article-title":"Loss of inositol polyphosphate 5-phosphatase is an early event in development of cutaneous squamous cell carcinoma","volume":"3","author":"A Sekulic","year":"2010","journal-title":"Cancer Prev Res (Phila)"},{"issue":"3","key":"pone.0223341.ref021","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.2353\/ajpath.2010.090816","article-title":"Loss of protein kinase C delta gene expression in human squamous cell carcinomas: a laser capture microdissection study","volume":"176","author":"V Yadav","year":"2010","journal-title":"Am J Pathol"},{"issue":"5","key":"pone.0223341.ref022","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1111\/j.0022-202X.2004.22501.x","article-title":"p16INK4a and p14ARF tumor suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma","volume":"122","author":"VL Brown","year":"2004","journal-title":"J Invest Dermatol"},{"issue":"3","key":"pone.0223341.ref023","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nm.2305","article-title":"Cancer epigenetics reaches mainstream oncology","volume":"17","author":"M Rodriguez-Paredes","year":"2011","journal-title":"Nat Med"},{"key":"pone.0223341.ref024","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-4419-9967-2_2","article-title":"DNA hypomethylation and hemimethylation in cancer","volume":"754","author":"M Ehrlich","year":"2013","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"pone.0223341.ref025","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.gde.2012.02.008","article-title":"Cancer epigenomics: beyond genomics","volume":"22","author":"J Sandoval","year":"2012","journal-title":"Curr Opin Genet Dev"},{"issue":"10","key":"pone.0223341.ref026","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1097\/01.MP.0000089779.35435.9D","article-title":"E-cadherin promoter hypermethylation in preneoplastic and neoplastic skin lesions","volume":"16","author":"MC Chiles","year":"2003","journal-title":"Mod Pathol"},{"issue":"5","key":"pone.0223341.ref027","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1111\/j.1365-2133.2006.07487.x","article-title":"Epigenetic abnormalities in cutaneous squamous cell carcinomas: frequent inactivation of the RB1\/p16 and p53 pathways","volume":"155","author":"K Murao","year":"2006","journal-title":"Br J Dermatol"},{"issue":"8","key":"pone.0223341.ref028","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1097\/01.LAB.0000025391.35798.F1","article-title":"Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma","volume":"82","author":"T Takeuchi","year":"2002","journal-title":"Lab Invest"},{"issue":"5","key":"pone.0223341.ref029","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/j.1365-2133.2009.09560.x","article-title":"FOXE1 is a target for aberrant methylation in cutaneous squamous cell carcinoma","volume":"162","author":"I Venza","year":"2010","journal-title":"Br J Dermatol"},{"key":"pone.0223341.ref030","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1186\/s12885-015-1650-x","article-title":"Secreted frizzled-related protein promotors are hypermethylated in cutaneous squamous carcinoma compared with normal epidermis","volume":"15","author":"J Liang","year":"2015","journal-title":"BMC Cancer"},{"issue":"7","key":"pone.0223341.ref031","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1002\/hed.23701","article-title":"Epigenetic alterations in metastatic cutaneous carcinoma","volume":"37","author":"OA Darr","year":"2015","journal-title":"Head Neck"},{"issue":"10","key":"pone.0223341.ref032","doi-asserted-by":"crossref","first-page":"e0164742","DOI":"10.1371\/journal.pone.0164742","article-title":"Silencing of ASC in Cutaneous Squamous Cell Carcinoma","volume":"11","author":"K Meier","year":"2016","journal-title":"PLoS One"},{"issue":"10","key":"pone.0223341.ref033","doi-asserted-by":"crossref","first-page":"e0187047","DOI":"10.1371\/journal.pone.0187047","article-title":"Silencing of G0\/G1 switch gene 2 in cutaneous squamous cell carcinoma","volume":"12","author":"Y Nobeyama","year":"2017","journal-title":"PLoS One"},{"issue":"2","key":"pone.0223341.ref034","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s12013-014-0507-2","article-title":"Aberrant Methylation Changes Detected in Cutaneous Squamous Cell Carcinoma of Immunocompetent Individuals","volume":"72","author":"L Li","year":"2015","journal-title":"Cell Biochem Biophys"},{"issue":"1","key":"pone.0223341.ref035","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12943-016-0537-z","article-title":"MiR-204 silencing in intraepithelial to invasive cutaneous squamous cell carcinoma progression","volume":"15","author":"A Toll","year":"2016","journal-title":"Mol Cancer"},{"key":"pone.0223341.ref036","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.humpath.2016.10.018","article-title":"DSS1 promoter hypomethylation and overexpression predict poor prognosis in melanoma and squamous cell carcinoma patients","volume":"60","author":"M Venza","year":"2017","journal-title":"Hum Pathol"},{"key":"pone.0223341.ref037","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev-med-111314-035900","article-title":"Epigenetic Therapeutics: A New Weapon in the War Against Cancer","volume":"67","author":"N Ahuja","year":"2016","journal-title":"Annu Rev Med"},{"issue":"10","key":"pone.0223341.ref038","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nmeth.2632","article-title":"Recommendations for the design and analysis of epigenome-wide association studies","volume":"10","author":"KB Michels","year":"2013","journal-title":"Nat Methods"},{"key":"pone.0223341.ref039","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13059-015-0644-y","article-title":"Age and sun exposure-related widespread genomic blocks of hypomethylation in nonmalignant skin","volume":"16","author":"AR Vandiver","year":"2015","journal-title":"Genome Biol"},{"issue":"1","key":"pone.0223341.ref040","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41467-018-03025-1","article-title":"Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin","volume":"9","author":"M Rodriguez-Paredes","year":"2018","journal-title":"Nat Commun"},{"key":"pone.0223341.ref041","volume-title":"AJCC Cancer Staging Manual","author":"MB Amin","year":"2007"},{"issue":"3","key":"pone.0223341.ref042","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2217\/epi.15.114","article-title":"Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences","volume":"8","author":"S Moran","year":"2016","journal-title":"Epigenomics"},{"issue":"6","key":"pone.0223341.ref043","doi-asserted-by":"crossref","first-page":"692","DOI":"10.4161\/epi.6.6.16196","article-title":"Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome","volume":"6","author":"J Sandoval","year":"2011","journal-title":"Epigenetics"},{"issue":"32","key":"pone.0223341.ref044","doi-asserted-by":"crossref","first-page":"4140","DOI":"10.1200\/JCO.2012.48.5516","article-title":"A prognostic DNA methylation signature for stage I non-small-cell lung cancer","volume":"31","author":"J Sandoval","year":"2013","journal-title":"J Clin Oncol"},{"issue":"2","key":"pone.0223341.ref045","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1467-9868.2005.00503.x","article-title":"Regularization and variable selection via the elastic net","volume":"67","author":"H Zou","year":"2005","journal-title":"Journal of the Royal Statistical Society: Series B (Statistical Methodology)"},{"issue":"7","key":"pone.0223341.ref046","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1080\/0266476042000214501","article-title":"Beta Regression for Modelling Rates and Proportions","volume":"31","author":"S Ferrari","year":"2004","journal-title":"Journal of Applied Statistics"},{"key":"pone.0223341.ref047","first-page":"315150","article-title":"ShinyGO: a graphical enrichment tool for animals and plants","author":"S Ge","year":"2018","journal-title":"bioRxiv"},{"issue":"9","key":"pone.0223341.ref048","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.jclinepi.2008.04.002","article-title":"The agreement chart as an alternative to the receiver-operating characteristic curve for diagnostic tests","volume":"61","author":"SI Bangdiwala","year":"2008","journal-title":"J Clin Epidemiol"},{"issue":"D1","key":"pone.0223341.ref049","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gky962","article-title":"New approach for understanding genome variations in KEGG","volume":"47","author":"M Kanehisa","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pone.0223341.ref050","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1053\/j.seminoncol.2005.07.001","article-title":"Aberrant DNA methylation in cutaneous malignancies","volume":"32","author":"R van Doorn","year":"2005","journal-title":"Semin Oncol"},{"issue":"2","key":"pone.0223341.ref051","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/ng.298","article-title":"The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores","volume":"41","author":"RA Irizarry","year":"2009","journal-title":"Nat Genet"},{"key":"pone.0223341.ref052","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-94-017-9211-0_2","volume-title":"Mutant p53 and MDM2 in Cancer","author":"K Inoue","year":"2014"},{"key":"pone.0223341.ref053","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3389\/fonc.2014.00285","article-title":"p53 Family and Cellular Stress Responses in Cancer","volume":"4","author":"J Pflaum","year":"2014","journal-title":"Front Oncol"},{"issue":"7","key":"pone.0223341.ref054","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1007\/s12094-017-1802-3","article-title":"Clinical implications of the deregulated TP73 isoforms expression in cancer","volume":"20","author":"N Rodriguez","year":"2018","journal-title":"Clin Transl Oncol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0223341","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,12,20]],"date-time":"2019-12-20T13:30:20Z","timestamp":1576848620000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0223341"}},"subtitle":[],"editor":[{"given":"Qian","family":"Tao","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2019,12,20]]},"references-count":54,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0223341","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/777227","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,20]]}}}