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Single cell transcriptomes of normal endometrial derived organoids uncover novel cell type markers and cryptic differentiation of primary tumours
Author(s) -
Cochrane Dawn R,
Campbell Kieran R,
Greening Kendall,
Ho Germain C,
Hopkins James,
Bui Minh,
Douglas J Maxwell,
Sharlandjieva Vassilena,
Munzur Aslı D,
Lai Daniel,
DeGrood Maya,
Gibbard Evan W,
Leung Samuel,
Boyd Niki,
Cheng Angela S,
Chow Christine,
Lim Jamie LP,
Farnell David A,
Kommoss Stefan,
Kommoss Friedrich,
Roth Andrew,
Hoang Lien,
McAlpine Jessica N,
Shah Sohrab P,
Huntsman David G
Publication year - 2020
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5511
Subject(s) - biology , transcriptome , endometrial cancer , organoid , immunohistochemistry , cell type , carcinoma , cancer research , endometrium , cell , stem cell marker , pathology , cancer , gene , gene expression , endocrinology , microbiology and biotechnology , immunology , medicine , genetics
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‐like and ciliated‐like 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‐specific 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. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.