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

Atiomo, William and Shafiee, Mohamad Nasir and Chapman, Caroline and Metzler, Veronika M. and Abouzeid, Jad and Latif, Ayşe and Chadwick, Amy and Kitson, Sarah and Sivalingam, Vanitha N. and Stratford, Ian J and Rutland, Catrin S. and Persson, Jenny L. and Ødum, Niels and Fuentes-Utrillia, Pablo and Jeyapalan, Jennie N. and Heery, David M. and Crosbie, Emma J. and Mongan, Nigel 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 . ISSN 1365-2265

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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<0.0001).

CONCLUSIONS: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: 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 / William Atiomo, Mohamad Nasir Shafiee, Caroline Chapman, Veronika M. Metzler, Jad Abouzeid, Ayşe Latif, Amy Chadwick, Sarah Kitson, Vanitha N. Sivalingam, Ian J. Stratford, Catrin S. Rutland, Jenny L. Persson, Niels Ødum1, Pablo Fuentes-Utrillia, Jennie N. Jeyapalan, David M. Heery, Emma J. Crosbie and Nigel P. Mongan, which has been published in final form at http://dx.doi.org/10.1111/cen.13436. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: Endometrial cancer, endometrium, polycystic ovary syndrome, NQO1
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Child Health, Obstetrics and Gynaecology
University of Nottingham, UK > Faculty of Science > School of Pharmacy
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Identification Number: 10.1111/cen.13436
Depositing User: Mongan, Nigel
Date Deposited: 01 Aug 2017 11:05
Last Modified: 06 Aug 2017 23:32
URI: http://eprints.nottingham.ac.uk/id/eprint/44499

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