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However, their roles in oral potentially malignant disorders (OPMDs) are unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive bioinformatic analysis was performed using publicly available datasets from chemically induced mouse OSCC models and human cohorts. The analysis included LOY\/EDY detection, gene set variation analysis (GSVA), PROGENy pathway profiling, cell\u2010to\u2010cell communication inference, and epigenetic correlation studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LOY was prevalent among men with OPMD, and EDY was identified in both mouse models and human OPMDs. The presence of LOY\/EDY was associated with a higher risk of OPMD progression to OSCC. Single\u2010cell analysis revealed that EDY\u2010positive epithelial cells exhibited elevated oncogenic pathway activity and enhanced IL17\u2010IL17RC signaling, possibly due to the loss of KDM5D in epithelial cells and altered epigenetic regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LOY\/EDY can be detected in OPMD and promotes malignant progression by altering oncogenic signaling and epithelial cell interactions. LOY\/EDY may serve as both a diagnostic biomarker and a therapeutic target, improving clinical management and patient outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hed.70070","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T09:06:33Z","timestamp":1761123993000},"page":"782-793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Loss of the Y Chromosome in Oral Potentially Premalignant Disorders Predicts Malignant Progression: An Integrative Cross\u2010Species Multi\u2010Cohort Bioinformatic Study"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8843-9938","authenticated-orcid":false,"given":"Rui","family":"Han","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Heidelberg University Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos B.","family":"Poell","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam Otolaryngology \u2010 Head and Neck Surgery  Amsterdam the Netherlands"},{"name":"Cancer Center Amsterdam Cancer Biology and Immunology  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Conde\u2010Lopez","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ) Heidelberg, Division of Radiooncology Radiobiology  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine University of Helsinki, Helsinki University Hospital  Helsinki Finland"},{"name":"Translational Immunology Research Program (TRIMM) University of Helsinki  Helsinki Finland"},{"name":"iCAN Digital Precision Cancer Medicine Flagship University of Helsinki  Helsinki Finland"},{"name":"Oral Pathology, Research Unit of Population Health, Faculty of Medicine University of Oulu  Oulu Finland"},{"name":"Medical Research Center, Oulu University Hospital University of Oulu  Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Kurth","sequence":"additional","affiliation":[{"name":"German Cancer Research Center (DKFZ) Heidelberg, Division of Radiooncology Radiobiology  Germany"},{"name":"German Cancer Research Center (DKFZ), and German Cancer Consortium (DKTK), Core Center Heidelberg  Heidelberg Germany"},{"name":"National Center for Radiation Research in Oncology (NCRO) Heidelberg Institute for Radiation Oncology (HIRO)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruud H.","family":"Brakenhoff","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, Vrije Universiteit Amsterdam Otolaryngology \u2010 Head and Neck Surgery  Amsterdam the Netherlands"},{"name":"Cancer Center Amsterdam Cancer Biology and Immunology  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3493-1711","authenticated-orcid":false,"given":"Jochen","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Cancer Research Center (DKFZ) Heidelberg, Division of Radiooncology Radiobiology  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djz232"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/1971080a0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541\u20107786.MCR\u201024\u20100105"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.05.014"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010018\u20100238\u20108"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201030759\u20101"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101765\u20103"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2966"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.06.006"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2023.02.024"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006234\u2010x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/odi.13704"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201036691\u2010x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2021.1898949"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mcb.2020.09.004"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201019401\u20109"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201022\u20102210"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.175141.114"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010023\u201001767\u2010y"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.276409.121"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioadv\/vbac016"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010024\u201001045\u20104"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201021246\u20109"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102105\u201014\u20107"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa1011"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326\u20106066.CIR\u201023\u20100133"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8321"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2021.1944554"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246\u2010023\u201000519\u2010y"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940\u20106207.CAPR\u201010\u20100155"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.4172\/2155\u20109899.1000230"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers7030827"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24129874"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713683.2015.1095933"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11102456"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.5b00333"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201020\u20101741"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006254\u20107"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940\u20106207.CAPR\u201013\u20100372"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010022\u201005973\u20109"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.25537"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ohn.421"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14071815"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2020.102986"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2022.105941"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmedinf.2024.105421"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010024\u201001198\u20105"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1515\/biol\u20102022\u20100747"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.857164"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI"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