{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:19:46Z","timestamp":1780575586838,"version":"3.54.1"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Extramammary Paget\u2019s disease (EMPD) is an intra-epidermal adenocarcinoma. Till now, the mechanisms underlying the pathogenesis of scrotal EMPD is poorly known. This present study aims to explore the knowledge of molecular mechanism of scrotal EMPD by identifying the hub genes and candidate drugs using integrated bioinformatics approaches. Firstly, the microarray datasets (GSE117285) were downloaded from the GEO database and then analyzed using GEO2R in order to obtain differentially expressed genes (DEGs). Moreover, hub genes were identified on the basis of their degree of connectivity using Cytohubba plugin of cytoscape tool. Finally, GEPIA and DGIdb were used for the survival analysis and selection of therapeutic candidates, respectively. A total of 786 DEGs were identified, of which 10 genes were considered as hub genes on the basis of the highest degree of connectivity. After the survival analysis of ten hub genes, a total of 5 genes were found to be altered in EMPD patients. Furthermore, 14 drugs of CHEK1, CCNA2, and CDK1 were found to have therapeutic potential against EMPD. This study updates the information and yields a new perspective in the context of understanding the pathogenesis of EMPD. In future, hub genes and candidate drugs might be capable of improving the personalized detection and therapies for EMPD.<\/jats:p>","DOI":"10.1371\/journal.pone.0254678","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T17:41:31Z","timestamp":1626975691000},"page":"e0254678","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Integrative bioinformatics approaches to map key biological markers and therapeutic drugs in Extramammary Paget\u2019s disease of the scrotum"],"prefix":"10.1371","volume":"16","author":[{"given":"Fatima","family":"Noor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Hamzah","family":"Saleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3540-4449","authenticated-orcid":true,"given":"Jen-Tsung","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Rizwan","family":"Javed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafa Abdullah","family":"Al-Megrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidra","family":"Aslam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"issue":"6","key":"pone.0254678.ref001","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/j.1610-0387.2010.07581.x","article-title":"Extramammary Paget disease\u2013clinical appearance, pathogenesis, management.","volume":"9","author":"G Wagner","year":"2011","journal-title":"JDDG: Journal der Deutschen Dermatologischen Gesellschaft"},{"issue":"3","key":"pone.0254678.ref002","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1463-1318.2004.00630.x","article-title":"Extramammary Paget\u2019s disease of the perianal region","volume":"6","author":"H Tulchinsky","year":"2004","journal-title":"Colorectal Disease"},{"issue":"10","key":"pone.0254678.ref003","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/S1726-4901(09)70425-3","article-title":"Extramammary Paget\u2019s disease of the scrotum associated with hepatocellular carcinoma.","volume":"72","author":"Y-C Li","year":"2009","journal-title":"J Chin Med Assoc"},{"issue":"4","key":"pone.0254678.ref004","doi-asserted-by":"crossref","DOI":"10.5070\/D3254043591","article-title":"Extramammary paget disease","volume":"25","author":"K St Claire","year":"2019","journal-title":"Dermatol Online J"},{"issue":"8","key":"pone.0254678.ref005","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1111\/ijd.14328","article-title":"Extramammary Paget\u2019s disease: a review of the literature","volume":"58","author":"RM Simonds","year":"2019","journal-title":"Int J Dermatol"},{"issue":"1","key":"pone.0254678.ref006","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1440-0960.2012.00898.x","article-title":"Extramammary Paget\u2019s disease of the vulva: an annotated review of the current literature","volume":"54","author":"ES Delport","year":"2013","journal-title":"Australas J Dermatol"},{"key":"pone.0254678.ref007","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/3768247","article-title":"Mammary and extramammary Paget\u2019s disease presented different expression pattern of steroid hormone receptors","volume":"2017","author":"S Zhou","year":"2017","journal-title":"BioMed research international"},{"issue":"5","key":"pone.0254678.ref008","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.urology.2008.06.043","article-title":"Primary scrotal cancer: disease characteristics and increasing incidence","volume":"72","author":"JL Wright","year":"2008","journal-title":"Urology"},{"issue":"5","key":"pone.0254678.ref009","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1245\/s10434-014-4139-y","article-title":"Extramammary Paget\u2019s disease in males: survival outcomes in 495 patients","volume":"22","author":"LA Herrel","year":"2015","journal-title":"Ann Surg Oncol"},{"issue":"4","key":"pone.0254678.ref010","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.det.2010.08.002","article-title":"Extramammary Paget\u2019s disease: summary of current knowledge","volume":"28","author":"C Lam","year":"2010","journal-title":"Dermatol Clin"},{"issue":"5","key":"pone.0254678.ref011","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/j.1365-4632.2010.04661.x","article-title":"A multicenter study on extramammary Paget\u2019s disease","volume":"50","author":"SJ Lee","year":"2011","journal-title":"Korea. 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