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Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with Polycystic Ovary Syndrome

Shafiee, Mohamad Nasir; Atiomo, William; Chapman, Caroline; Metzler, Veronika M.; Abouzeid, Jad; Latif, Ayşe; Chadwick, Amy; Stratford, Ian J.; Kitson, Sarah; Sivalingam, Vanitha N.; Rutland, Catrin S.; Persson, Jenny L.; Fuentes-Utrillia, Pablo; Ødum, Niels; Jeyapalan, Jennie N.; Heery, David M.; Crosbie, Emma J.; Mongan, Nigel P.

Authors

Mohamad Nasir Shafiee

William Atiomo

Veronika M. Metzler

Jad Abouzeid

Ayşe Latif

Amy Chadwick

Ian J. Stratford

Sarah Kitson

Vanitha N. Sivalingam

Catrin S. Rutland

Jenny L. Persson

Pablo Fuentes-Utrillia

Niels Ødum

Jennie N. Jeyapalan

David M. Heery

Emma J. Crosbie

Nigel P. Mongan



Abstract

OBJECTIVE: Women with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC).
AIM: To investigate whether the endometrium of women with PCOS possess gene expression changes similar to those found in EC.
DESIGN AND METHODS: Patients with EC, PCOS and control women unaffected by either PCOS or EC were recruited into a cross-sectional study at the Nottingham University Hospital, UK. For RNA sequencing, representative individual endometrial biopsies were obtained from women with EC, PCOS and a woman unaffected by PCOS or EC. Expression of a subset of differentially expressed genes identified by RNA sequencing, including NAD(P)H quinone dehydrogenase 1 (NQO1), were validated by quantitative reverse transcriptase PCR validation (n=76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing dataset (n=381). The expression of NQO1 was validated by immuno-histochemistry in EC samples from a separate cohort (n=91) 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 was obtained for the study.
RESULTS: We show for the first that that NQO1 expression is significantly increased in the endometrium of women with PCOS and EC. Immunohistochemistry confirms significantly increased NQO1 protein expression in EC relative to non-malignant endometrial tissue (p

Journal Article Type Article
Publication Date 2017-11
Journal Clinical Endocrinology
Print ISSN 0300-0664
Electronic ISSN 1365-2265
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 87
Issue 5
Pages 557-565
APA6 Citation Atiomo, W., Shafiee, M. N., Chapman, C., Metzler, V. M., Abouzeid, J., Latif, A., …Mongan, N. P. (2017). Expression of NAD(P)H quinone dehydrogenase 1 (NQO1) is increased in the endometrium of women with endometrial cancer and women with Polycystic Ovary Syndrome. Clinical Endocrinology, 87(5), 557-565. https://doi.org/10.1111/cen.13436
DOI https://doi.org/10.1111/cen.13436
Keywords Endometrial cancer, endometrium, polycystic ovary syndrome, NQO1
Publisher URL http://onlinelibrary.wiley.com/doi/10.1111/cen.13436/abstract
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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