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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.
Clin Endocrinol (Oxf) 2017; 87(5):557-565CE

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 possesses 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), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry 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 were obtained for the study.

RESULTS

We show for the first 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 nonmalignant endometrial tissue (P < .0001).

CONCLUSIONS

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

Authors+Show Affiliations

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.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. Faculty of Medicine, Department Obstetrics and Gynaecology, UKM Medical Centre, Cheras, Kuala Lumpur, Malaysia.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.Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK.Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK.Faculty of Biology, Medicine and Health, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK.Faculty of Biology, Division of Molecular & Clinical Cancer Sciences, Medicine and Health, University of Manchester, Manchester, UK.Faculty of Biology, Division of Molecular & Clinical Cancer Sciences, Medicine and Health, University of Manchester, Manchester, UK. Department of Obstetrics and Gynaecology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. Manchester School of Pharmacy, University of Manchester, Manchester, UK.Faculty of Biology, Division of Molecular & Clinical Cancer Sciences, Medicine and Health, University of Manchester, Manchester, UK. Department of Obstetrics and Gynaecology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. Manchester School of Pharmacy, University of Manchester, Manchester, UK.Faculty of Biology, Medicine and Health, Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK.Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK.Clinical Research Center, Lund University, Malmö, Sweden. Department of Molecular Bology, Umeå University, Umeå, Sweden.Department of Immunology and Microbiology, University of Copenhagen, Kobenhavn, Denmark.Edinburgh Genomics, University of Edinburgh, Edinburgh, UK.Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK.School of Pharmacy, University of Nottingham, Nottingham, UK.Faculty of Biology, Division of Molecular & Clinical Cancer Sciences, Medicine and Health, University of Manchester, Manchester, UK. Department of Obstetrics and Gynaecology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. Manchester School of Pharmacy, University of Manchester, Manchester, UK.Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham, Nottingham, UK. Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28748640

Citation

Atiomo, William, et al. "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, vol. 87, no. 5, 2017, pp. 557-565.
Atiomo W, Shafiee MN, Chapman C, et al. 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. Clin Endocrinol (Oxf). 2017;87(5):557-565.
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), pp. 557-565. doi:10.1111/cen.13436.
Atiomo W, et al. 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. Clin Endocrinol (Oxf). 2017;87(5):557-565. PubMed PMID: 28748640.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Atiomo,William, AU - Shafiee,Mohamad Nasir, AU - Chapman,Caroline, AU - Metzler,Veronika M, AU - Abouzeid,Jad, AU - Latif,Ayşe, AU - Chadwick,Amy, AU - Kitson,Sarah, AU - Sivalingam,Vanitha N, AU - Stratford,Ian J, AU - Rutland,Catrin S, AU - Persson,Jenny L, AU - Ødum,Niels, AU - Fuentes-Utrilla,Pablo, AU - Jeyapalan,Jennie N, AU - Heery,David M, AU - Crosbie,Emma J, AU - Mongan,Nigel P, Y1 - 2017/08/18/ PY - 2017/01/09/received PY - 2017/05/11/revised PY - 2017/07/24/accepted PY - 2017/7/28/pubmed PY - 2018/6/30/medline PY - 2017/7/28/entrez KW - NQO1 KW - endometrial cancer KW - endometrium KW - polycystic ovary syndrome SP - 557 EP - 565 JF - Clinical endocrinology JO - Clin. Endocrinol. (Oxf) VL - 87 IS - 5 N2 - 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 possesses 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), was validated by quantitative reverse transcriptase PCR validation (n = 76) and in the cancer genome atlas UCEC (uterine corpus endometrioid carcinoma) RNA sequencing data set (n = 381). The expression of NQO1 was validated by immunohistochemistry 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 were obtained for the study. RESULTS: We show for the first 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 nonmalignant endometrial tissue (P < .0001). CONCLUSIONS: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1. SN - 1365-2265 UR - https://www.unboundmedicine.com/medline/citation/28748640/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_ L2 - https://doi.org/10.1111/cen.13436 DB - PRIME DP - Unbound Medicine ER -