Advanced

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. and Stratford, Ian J., et al. (2017) In Clinical Endocrinology 87(5). p.557-565
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
endometrial cancer, endometrium, NQO1, polycystic ovary syndrome
in
Clinical Endocrinology
volume
87
issue
5
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85032221854
  • pmid:28748640
  • wos:000413762200020
ISSN
0300-0664
DOI
10.1111/cen.13436
language
English
LU publication?
yes
id
5dc47e69-c983-457c-a82f-cf1eb38c432b
date added to LUP
2017-11-12 16:29:21
date last changed
2018-05-29 11:13:10
@article{5dc47e69-c983-457c-a82f-cf1eb38c432b,
  abstract     = {<p>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 &lt;.0001). Conclusions: The results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.</p>},
  author       = {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-Utrilla, Pablo and Jeyapalan, Jennie N. and Heery, David M and Crosbie, Emma J. and Mongan, Nigel P.},
  issn         = {0300-0664},
  keyword      = {endometrial cancer,endometrium,NQO1,polycystic ovary syndrome},
  language     = {eng},
  month        = {11},
  number       = {5},
  pages        = {557--565},
  publisher    = {Wiley-Blackwell},
  series       = {Clinical Endocrinology},
  title        = {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},
  url          = {http://dx.doi.org/10.1111/cen.13436},
  volume       = {87},
  year         = {2017},
}