{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:46:59Z","timestamp":1791287219909,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    We aimed to estimate the diagnostic value of DNA methylation levels in cytological samples of endometrial cancer (EC) and atypical hyperplasia (AH). Two hypermethylated genes, namely, cysteine dioxygenase type 1 (\n                    <jats:italic>CDO1<\/jats:italic>\n                    ) and zinc finger protein 454 (\n                    <jats:italic>ZNF454<\/jats:italic>\n                    ), in patients with EC were identified from The Cancer Genome Atlas database. In 103 endometrial histological specimens (the training set), the methylation levels of candidate genes were verified by quantitative methylation-specific polymerase chain reaction (qMSP). The methylation levels of another 120 cytological specimens (the testing set) were evaluated. Sensitivity (Se), specificity (Sp), accuracy, and area under the curve (AUC) were determined, with diagnosis verified by histopathological results.\n                    <jats:italic>CDO1<\/jats:italic>\n                    and\n                    <jats:italic>ZNF454<\/jats:italic>\n                    verified hypermethylation in histological specimens of patients with EC and AH compared with those with benign and normal endometrium (\n                    <jats:italic>P<\/jats:italic>\n                    &amp;lt; 0.001). In cytological specimens, hypermethylated\n                    <jats:italic>CDO1<\/jats:italic>\n                    showed 86.36% Se and 90.79% Sp with the cutoff value of 6.0 to distinguish between malignant and benign groups;\n                    <jats:italic>ZNF454<\/jats:italic>\n                    showed 79.55% Se and 93.42% Sp with the cutoff value of 7.1. When the two genes were combined, Se increased to 90.91% and Sp was 86.84%. AUC reached 0.931 (95% CI: 0.885\u20130.976). The diagnostic accuracy with cytology had no significant difference with endometrial tissue (\n                    <jats:italic>P<\/jats:italic>\n                    = 0.847 for\n                    <jats:italic>CDO1<\/jats:italic>\n                    ,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.108 for\n                    <jats:italic>ZNF454<\/jats:italic>\n                    , and\n                    <jats:italic>P<\/jats:italic>\n                    = 0.665 for their combination). Hypermethylated\n                    <jats:italic>CDO1<\/jats:italic>\n                    and\n                    <jats:italic>ZNF454<\/jats:italic>\n                    in endometrial cytology showed high Se, Sp, and AUC to detect EC and AH. Methylation analysis of endometrial cytology is promising biomarker for the screening of EC and AH.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2022.714663","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T02:26:36Z","timestamp":1651112796000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Hypermethylated CDO1 and ZNF454 in Cytological Specimens as Screening Biomarkers for Endometrial Cancer"],"prefix":"10.3389","volume":"12","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangkang","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanbo","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianglu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"B1","volume-title":"Uterine Cancer","author":"Faizan","year":"2021"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2020.31.e22","article-title":"Survival and Recurrence in Stage II Endometrial Cancers in Relation to Uterine Risk Stratification After Introduction of Lymph Node Resection and Omission of Postoperative Radiotherapy: A Danish Gynecological Cancer Group Study","volume":"31","author":"Ortoft","year":"2020","journal-title":"J Gynecol Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21565","article-title":"Cancer Treatment and Survivorship Statistics, 2019","volume":"69","author":"Miller","year":"2019","journal-title":"CA Cancer J Clin"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7292(06)60031-3","article-title":"Carcinoma of the Corpus Uteri","volume":"95","author":"Creasman","year":"2006","journal-title":"Int J Gynaecol Obstet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2011.06.023","article-title":"Endometrial Hyperplasia - the Dilemma of Management Remains: A Retrospective Observational Study of 280 Women","volume":"159","author":"Daud","year":"2011","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.bpobgyn.2019.12.006","article-title":"Current and Future Approaches to Screening for Endometrial Cancer","volume":"65","author":"Gentry-Maharaj","year":"2020","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32514","article-title":"New Perspectives on Screening and Early Detection of Endometrial Cancer","volume":"145","author":"Costas","year":"2019","journal-title":"Int J Cancer"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.5468\/ogs.2019.62.6.445","article-title":"Endometrial Thickness Cut-Off Value by Transvaginal Ultrasonography for Screening of Endometrial Pathology in Premenopausal and Postmenopausal Women","volume":"62","author":"Park","year":"2019","journal-title":"Obstet Gynecol Sci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.13342","article-title":"Reappraisal of Endometrial Thickness for the Detection of Endometrial Cancer in Postmenopausal Bleeding: A Retrospective Cohort Study","volume":"123","author":"Wong","year":"2016","journal-title":"BJOG"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2015.12.008","article-title":"The Accuracy of Endometrial Sampling in Women With Postmenopausal Bleeding: A Systematic Review and Meta-Analysis","volume":"197","author":"van Hanegem","year":"2016","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/jog.13998","article-title":"Hysteroscopic Morphological Pattern Reflects Histological Grade of Endometrial Cancer","volume":"45","author":"Miyamoto","year":"2019","journal-title":"J Obstet Gynaecol Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000002261","article-title":"Accuracy of Endometrial Sampling in Endometrial Carcinoma: A Systematic Review and Meta-Analysis","volume":"130","author":"Visser","year":"2017","journal-title":"Obstet Gynecol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/his.12249","article-title":"Reproducibility of Current Classifications of Endometrial Endometrioid Glandular Proliferations: Further Evidence Supporting a Simplified Classification","volume":"64","author":"Ordi","year":"2014","journal-title":"Histopathol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.61.3083","article-title":"Lavage of the Uterine Cavity for Molecular Detection of Mullerian Duct Carcinomas: A Proof-Of-Concept Study","volume":"33","author":"Maritschnegg","year":"2015","journal-title":"J Clin Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S225672","article-title":"The Value of DNA Quantitative Cytology Test for the Screening of Endometrial Cancer","volume":"11","author":"Yang","year":"2019","journal-title":"Cancer Manag Res"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00067","article-title":"An Efficacious Endometrial Sampler for Screening Endometrial Cancer","volume":"9","author":"Han","year":"2019","journal-title":"Front Oncol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10238-017-0467-0","article-title":"DNA Methylation Profiles in Cancer Diagnosis and Therapeutics","volume":"18","author":"Pan","year":"2018","journal-title":"Clin Exp Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1703577114","article-title":"DNA Methylation Markers for Diagnosis and Prognosis of Common Cancers","volume":"114","author":"Hao","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1186\/s12885-018-5125-8","article-title":"Performance of a DNA Methylation Marker Panel Using Liquid-Based Cervical Scrapes to Detect Cervical Cancer and its Precancerous Stages","volume":"18","author":"Schmitz","year":"2018","journal-title":"BMC Cancer"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2021.09.007","article-title":"Upper Urothelial Tract High-Grade Carcinoma: Comparison of Urine Cytology and DNA Methylation Analysis in Urinary Samples","volume":"118","author":"Pierconti","year":"2021","journal-title":"Hum Pathol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-1019","article-title":"Histone-Related Genes Are Hypermethylated in Lung Cancer and Hypermethylated HIST1H4F Could Serve as a Pan-Cancer Biomarker","volume":"79","author":"Dong","year":"2019","journal-title":"Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0863","article-title":"Integrated Epigenomics Analysis Reveals a DNA Methylation Panel for Endometrial Cancer Detection Using Cervical Scrapings","volume":"23","author":"Huang","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.12.023","article-title":"Analysis of DNA Methylation in Endometrial Biopsies to Predict Risk of Endometrial Cancer","volume":"156","author":"Multinu","year":"2020","journal-title":"Gynecol Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-018-0489-2","article-title":"Gene Promoter Methylation in Endometrial Carcinogenesis","volume":"25","author":"Cornel","year":"2019","journal-title":"Pathol Oncol Res"},{"key":"B25","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/nature12113","article-title":"Integrated Genomic Characterization of Endometrial Carcinoma","volume":"497","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4103\/0301-4738.71699","article-title":"A Simple Nomogram for Sample Size for Estimating Sensitivity and Specificity of Medical Tests","volume":"58","author":"Malhotra","year":"2010","journal-title":"Indian J Ophthalmol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2020.10933","article-title":"Methylationdriven Genes PMPCAP1, SOWAHC and ZNF454 as Potential Prognostic Biomarkers in Lung Squamous Cell Carcinoma","volume":"21","author":"Zhu","year":"2020","journal-title":"Mol Med Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2956","article-title":"Identification of Aberrantly Methylated Differentially Expressed Genes and Associated Pathways in Endometrial Cancer Using Integrated Bioinformatic Analysis","volume":"9","author":"Liu","year":"2020","journal-title":"Cancer Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S272755","article-title":"A Clinical Comparative Study of Two Different Endometrial Cell Samplers for Evaluation of Endometrial Lesions by Cytopathological Diagnosis","volume":"12","author":"Lv","year":"2020","journal-title":"Cancer Manag Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.ygyno.2015.01.552","article-title":"Detection of Endometrial Cancer via Molecular Analysis of DNA Collected With Vaginal Tampons","volume":"137","author":"Bakkum-Gamez","year":"2015","journal-title":"Gynecol Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28843","article-title":"Discovery and Validation of Methylation Markers for Endometrial Cancer","volume":"135","author":"Wentzensen","year":"2014","journal-title":"Int J Cancer"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23480","article-title":"The Diagnostic Role of DNA Methylation in Sporadic Endometrial Cancer: A Systematic Review and Meta-Analysis","volume":"9","author":"Fan","year":"2018","journal-title":"Oncotarget"},{"key":"B33","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s13148-019-0765-3","article-title":"Combined Genetic Mutations and DNA-Methylated Genes as Biomarkers for Endometrial Cancer Detection From Cervical Scrapings","volume":"11","author":"Liew","year":"2019","journal-title":"Clin Epigenetics"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2020-0164","article-title":"DNA Methylation Markers for Endometrial Cancer Detection in Minimally Invasive Samples: A Systematic Review","volume":"12","author":"den Helder","year":"2020","journal-title":"Epigenomics"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.11.028","article-title":"Combining Copy Number, Methylation Markers, and Mutations as a Panel for Endometrial Cancer Detection via Intravaginal Tampon Collection","volume":"156","author":"Sangtani","year":"2020","journal-title":"Gynecol Oncol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2018.29.e17","article-title":"The Feasibility of Detecting Endometrial and Ovarian Cancer Using DNA Methylation Biomarkers in Cervical Scrapings","volume":"29","author":"Chang","year":"2018","journal-title":"J Gynecol Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s13148-020-00958-7","article-title":"Non-Invasive Detection of Endometrial Cancer by DNA Methylation Analysis in Urine","volume":"12","author":"van den Helder","year":"2020","journal-title":"Clin Epigenetics"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/cyt.12364","article-title":"Morphometric Analysis of Endometrial Cells in Liquid-Based Cervical Cytology Samples","volume":"28","author":"Gupta","year":"2017","journal-title":"Cytopathol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s00432-019-03093-w","article-title":"DNA Methylation-Based Profiling of Uterine Neoplasms: A Novel Tool to Improve Gynecologic Cancer Diagnostics","volume":"146","author":"Kommoss","year":"2020","journal-title":"J Cancer Res Clin Oncol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1080\/15592294.2016.1252891","article-title":"Epigenetic Changes as Prognostic Predictors in Endometrial Carcinomas","volume":"12","author":"Farkas","year":"2017","journal-title":"Epigenetics"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.714663\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T02:26:41Z","timestamp":1651112801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.714663\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":40,"alternative-id":["10.3389\/fonc.2022.714663"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.714663","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,28]]},"article-number":"714663"}}