{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T23:58:15Z","timestamp":1768435095982,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,8,18]],"date-time":"2017-08-18T00:00:00Z","timestamp":1503014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/1024291\/1"],"award-info":[{"award-number":["BB\/1024291\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000837","name":"University of Nottingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000771","name":"Prostate Cancer UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000771","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["NIHR\u2010CS\u2010012\u2010009"],"award-info":[{"award-number":["NIHR\u2010CS\u2010012\u2010009"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Women with a prior history of polycystic ovary syndrome (<jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>) have an increased risk of endometrial cancer (<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate whether the endometrium of women with<jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>possesses gene expression changes similar to those found in<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Methods<\/jats:title><jats:p>Patients with<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>and control women unaffected by either<jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>or<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>were recruited into a cross\u2010sectional study at the Nottingham University Hospital,<jats:styled-content style=\"fixed-case\">UK<\/jats:styled-content>. For<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>sequencing, representative individual endometrial biopsies were obtained from women with<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>and a woman unaffected by<jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>or<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>. Expression of a subset of differentially expressed genes identified by<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>sequencing, including<jats:styled-content style=\"fixed-case\">NAD<\/jats:styled-content>(P)H quinone dehydrogenase 1 (<jats:italic><jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content>1<\/jats:italic>), was validated by quantitative reverse transcriptase<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>validation (n\u00a0=\u00a076) and in the cancer genome atlas<jats:styled-content style=\"fixed-case\">UCEC<\/jats:styled-content>(uterine corpus endometrioid carcinoma)<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>sequencing data set (n\u00a0=\u00a0381). The expression of<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content>1 was validated by immunohistochemistry in<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>samples from a separate cohort (n\u00a0=\u00a091) comprised of consecutive patients who underwent hysterectomy at St Mary's Hospital, Manchester, between 2011 and 2013. A further 6 postmenopausal women with histologically normal endometrium who underwent hysterectomy for genital prolapse were also included. Informed consent and local ethics approval were obtained for the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We show for the first that<jats:italic><jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content>1<\/jats:italic>expression is significantly increased in the endometrium of women with<jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>. Immunohistochemistry confirms significantly increased<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content>1 protein expression in<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>relative to nonmalignant endometrial tissue (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a0.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results obtained here support a previously unrecognized molecular link between<jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">EC<\/jats:styled-content>involving<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content>1.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.13436","type":"journal-article","created":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T08:26:38Z","timestamp":1501143998000},"page":"557-565","source":"Crossref","is-referenced-by-count":14,"title":["Expression of<scp>NAD<\/scp>(P)H quinone dehydrogenase 1 (<scp>NQO<\/scp>1) is increased in the endometrium of women with endometrial cancer and women with polycystic ovary syndrome"],"prefix":"10.1111","volume":"87","author":[{"given":"William","family":"Atiomo","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Health Sciences Division of Obstetrics and Gynaecology and Child Health School of Medicine Queen's Medical Centre Nottingham University Hospital Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamad Nasir","family":"Shafiee","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences Division of Obstetrics and Gynaecology and Child Health School of Medicine Queen's Medical Centre Nottingham University Hospital Nottingham UK"},{"name":"Faculty of Medicine Department Obstetrics and Gynaecology UKM Medical Centre Cheras Kuala Lumpur Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Chapman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences Division of Obstetrics and Gynaecology and Child Health School of Medicine Queen's Medical Centre Nottingham University Hospital Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronika M.","family":"Metzler","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences School of Veterinary Medicine and Science University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jad","family":"Abouzeid","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences School of Veterinary Medicine and Science University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ay\u015fe","family":"Latif","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health Division of Pharmacy and Optometry School of Health Sciences University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Chadwick","sequence":"additional","affiliation":[{"name":"Faculty of Biology Division of Molecular &amp; Clinical Cancer Sciences Medicine and Health University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Kitson","sequence":"additional","affiliation":[{"name":"Faculty of Biology Division of Molecular &amp; Clinical Cancer Sciences Medicine and Health University of Manchester Manchester UK"},{"name":"Department of Obstetrics and Gynaecology Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester UK"},{"name":"Manchester School of Pharmacy University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanitha N.","family":"Sivalingam","sequence":"additional","affiliation":[{"name":"Faculty of Biology Division of Molecular &amp; Clinical Cancer Sciences Medicine and Health University of Manchester Manchester UK"},{"name":"Department of Obstetrics and Gynaecology Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester UK"},{"name":"Manchester School of Pharmacy University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian J.","family":"Stratford","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health Division of Pharmacy and Optometry School of Health Sciences University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catrin S.","family":"Rutland","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences School of Veterinary Medicine and Science University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny L.","family":"Persson","sequence":"additional","affiliation":[{"name":"Clinical Research Center Lund University Malm\u00f6 Sweden"},{"name":"Department of Molecular Bology Ume\u00e5 University Ume\u00e5 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"\u00d8dum","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology University of Copenhagen Kobenhavn Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Fuentes\u2010Utrilla","sequence":"additional","affiliation":[{"name":"Edinburgh Genomics University of Edinburgh Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennie N.","family":"Jeyapalan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences School of Veterinary Medicine and Science University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Heery","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Nottingham Nottingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma J.","family":"Crosbie","sequence":"additional","affiliation":[{"name":"Faculty of Biology Division of Molecular &amp; Clinical Cancer Sciences Medicine and Health University of Manchester Manchester UK"},{"name":"Department of Obstetrics and Gynaecology Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester UK"},{"name":"Manchester School of Pharmacy University of Manchester Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5438-1126","authenticated-orcid":false,"given":"Nigel P.","family":"Mongan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences School of Veterinary Medicine and Science University of Nottingham Nottingham UK"},{"name":"Department of Pharmacology Weill Cornell Medicine New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21332"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-10-0832"},{"key":"e_1_2_8_4_1","first-page":"ED000095","article-title":"The emerging epidemic of endometrial cancer: time to take action","volume":"12","author":"Crosbie E","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der102"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des232"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2014.07.111"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des042"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmu012"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2013.06.032"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2016.01.019"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.13106"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2013.777416"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev055"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12113"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.016"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.4572.1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.05.042"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-015-0030-9"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/1464727002000198781"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-010-9658-7"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2013.10.028"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2008.12.018"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0074"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-0508"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2012.12.019"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052706799"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(04)82008-1"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(04)82019-6"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.01996.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/S0026-895X(25)13321-X","article-title":"pH\u2010dependent inactivation of DT\u2010diaphorase by mitomycin C and porfiromycin","volume":"44","author":"Siegel D","year":"1993","journal-title":"Mol Pharmacol"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3157"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.357"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.155"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-011-1629-5"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1271-4"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1227-8"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702176104"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21194"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.39.25443"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-011-9144-9"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1068537"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2011.05.001"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.10.011"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1204"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.13436","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.13436","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T18:18:17Z","timestamp":1750789097000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.13436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,18]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1111\/cen.13436"],"URL":"https:\/\/doi.org\/10.1111\/cen.13436","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,18]]}}}