{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:34:47Z","timestamp":1790620487808,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,8,22]],"date-time":"2020-08-22T00:00:00Z","timestamp":1598054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000015","name":"Canadian Cancer Society Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000015","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endometrial carcinoma, the most common gynaecological cancer, develops from endometrial epithelium which is composed of secretory and ciliated cells. Pathologic classification is unreliable and there is a need for prognostic tools. We used single cell sequencing to study organoid model systems derived from normal endometrial endometrium to discover novel markers specific for endometrial ciliated or secretory cells. A marker of secretory cells (MPST) and several markers of ciliated cells (FAM92B, WDR16, and DYDC2) were validated by immunohistochemistry on organoids and tissue sections. We performed single cell sequencing on endometrial and ovarian tumours and found both secretory\u2010like and ciliated\u2010like tumour cells. We found that ciliated cell markers (DYDC2, CTH, FOXJ1, and p73) and the secretory cell marker MPST were expressed in endometrial tumours and positively correlated with disease\u2010specific and overall survival of endometrial cancer patients. These findings suggest that expression of differentiation markers in tumours correlates with less aggressive disease, as would be expected for tumours that retain differentiation capacity, albeit cryptic in the case of ciliated cells. These markers could be used to improve the risk stratification of endometrial cancer patients, thereby improving their management. We further assessed whether consideration of MPST expression could refine the ProMiSE molecular classification system for endometrial tumours. We found that higher expression levels of MPST could be used to refine stratification of three of the four ProMiSE molecular subgroups, and that any level of MPST expression was able to significantly refine risk stratification of the copy number high subgroup which has the worst prognosis. Taken together, this shows that single cell sequencing of putative cells of origin has the potential to uncover novel biomarkers that could be used to guide management of cancers. \u00a9 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.5511","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T02:07:46Z","timestamp":1595210866000},"page":"201-214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Single cell transcriptomes of normal endometrial derived organoids uncover novel cell type markers and cryptic differentiation of primary tumours"],"prefix":"10.1002","volume":"252","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1523-9351","authenticated-orcid":false,"given":"Dawn R","family":"Cochrane","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kieran R","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendall","family":"Greening","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germain C","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh","family":"Bui","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Maxwell","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilena","family":"Sharlandjieva","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asl\u0131 D","family":"Munzur","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"DeGrood","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3946-4457","authenticated-orcid":false,"given":"Evan W","family":"Gibbard","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Leung","sequence":"additional","affiliation":[{"name":"Genetic Pathology Evaluation Centre Vancouver General Hospital  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki","family":"Boyd","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela S","family":"Cheng","sequence":"additional","affiliation":[{"name":"Genetic Pathology Evaluation Centre Vancouver General Hospital  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Chow","sequence":"additional","affiliation":[{"name":"Genetic Pathology Evaluation Centre Vancouver General Hospital  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie LP","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center  New York City NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Farnell","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology Vancouver General Hospital  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kommoss","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Kommoss","sequence":"additional","affiliation":[{"name":"Institute of Pathology Medizin Campus Bodensee  Friedrichshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lien","family":"Hoang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica N","family":"McAlpine","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohrab P","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center  New York City NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G","family":"Huntsman","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology BC Cancer Agency  Vancouver BC Canada"},{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver BC Canada"},{"name":"Department of Medical Genetics University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0470019"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(68)90317-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0420537"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2018.07.027"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006250-196802000-00011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","unstructured":"ZhangS ZhangT DolgalevI et al. Both fallopian tube and ovarian surface epithelium can act as cell\u2010of\u2010origin for high grade serous ovarian cancer.bioRxiv2019; 481200. Not peer reviewed.","DOI":"10.1101\/481200"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70591-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv306"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2015.09.023"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(11)70404-1"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdp120"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2001.6276"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2003.11.048"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3802\/jgo.2015.26.1.32"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181b96ec6"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.01.023"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31827f576a"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31828c63ed"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12029"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60442-5"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0000000000000488"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12113"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2878"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.43"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.190"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30496"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy058"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.82"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2016.07.090"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.029249"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9989"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2018.08.021"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00978"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00170.2003"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00830"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0414-6"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14100"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11004-7"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00160-16"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04500.x"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.05.061"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0529-1"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep34949"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0000000000000609"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5314"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2214-z"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.149989"},{"key":"e_1_2_8_49_1","unstructured":"HuZ ArtibaniM AlsaadiA et al. The repertoire of serous ovarian cancer non\u2010genetic heterogeneity revealed by single\u2010cell sequencing of normal fallopian tube epithelial cells.bioRxiv2019; 672626v1. Not peer reviewed."},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-018-0597-6"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy244"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.495"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.13727"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67063-8"},{"key":"e_1_2_8_55_1","first-page":"47","article-title":"Carcinoma of the corpus uteri","volume":"6","author":"Creasman WT","year":"2001","journal-title":"J Epidemiol Biostat"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199608293350907"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2014.02.012"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2019.06.012"},{"key":"e_1_2_8_59_1","doi-asserted-by":"crossref","unstructured":"BergenV LangeM PeidliS et al. Generalizing RNA velocity to transient cell states through dynamical modeling.bioRxiv2019; 820936v1. Not peer reviewed.","DOI":"10.1101\/820936"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02289-3"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.233"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12168"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0206785"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142956.cy0623s36"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.16.3132"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307893"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001216"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-10-51"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.5511","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5511","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.5511","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.5511","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:23:08Z","timestamp":1761052988000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.5511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,22]]},"references-count":68,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1002\/path.5511"],"URL":"https:\/\/doi.org\/10.1002\/path.5511","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,22]]},"assertion":[{"value":"2020-03-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}