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 Ødum, Pablo Fuentes-Utrilla, Jennie N. Jeyapalan, David M. Heery, Emma J. Crosbie, Nigel P. Mongan

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)557-565
Number of pages9
JournalClinical Endocrinology
Volume87
Issue number5
DOIs
Publication statusPublished - 1 Nov 2017

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NAD(P)H Dehydrogenase (Quinone)
Polycystic Ovary Syndrome
Endometrial Neoplasms
Endometrium
Ovarian Neoplasms
RNA Sequence Analysis
Hysterectomy
Immunohistochemistry
Endometrioid Carcinoma
Atlases
Prolapse
Reverse Transcriptase Polymerase Chain Reaction
Informed Consent
Ethics
Cross-Sectional Studies
Genome

Keywords

  • endometrial cancer
  • endometrium
  • NQO1
  • polycystic ovary syndrome

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

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

In: Clinical Endocrinology, Vol. 87, No. 5, 01.11.2017, p. 557-565.

Research output: Contribution to journalArticle

Atiomo, W, Shafiee, MN, Chapman, C, Metzler, VM, Abouzeid, J, Latif, A, Chadwick, A, Kitson, S, Sivalingam, VN, Stratford, IJ, Rutland, CS, Persson, JL, Ødum, N, Fuentes-Utrilla, P, Jeyapalan, JN, Heery, DM, Crosbie, EJ & Mongan, NP 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, vol. 87, no. 5, pp. 557-565. https://doi.org/10.1111/cen.13436
Atiomo, William ; Shafiee, Mohamad Nasir ; Chapman, Caroline ; Metzler, Veronika M. ; Abouzeid, Jad ; Latif, Ayşe ; Chadwick, Amy ; Kitson, Sarah ; Sivalingam, Vanitha N. ; Stratford, Ian J. ; Rutland, Catrin S. ; Persson, Jenny L. ; Ødum, Niels ; Fuentes-Utrilla, Pablo ; Jeyapalan, Jennie N. ; Heery, David M. ; Crosbie, Emma J. ; Mongan, Nigel P. / 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. In: Clinical Endocrinology. 2017 ; Vol. 87, No. 5. pp. 557-565.
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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 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.",
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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.

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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.

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