Year-end Sale % OFF 
Abstract
SummaryObjectiveWomen with a prior history of polycystic ovary syndrome (PCOS) have an increased risk of endometrial cancer (EC).AimTo investigate whether the endometrium of women with PCOS possesses gene expression changes similar to those found in EC.Design and MethodsPatients 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.ResultsWe 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).ConclusionsThe results obtained here support a previously unrecognized molecular link between PCOS and EC involving NQO1.
Highlights
Endometrial cancer (EC) is the most common gynaecological cancer affecting women in the United States, with an estimated 60 050 new cases in 2016.1 The incidence of EC has increased by over 65% since the late 1970s correlating with rising incidence of obesity and increased longevity.[2,3] EC is usually treated by hysterectomy, but surgery carries increased risk in obese women and renders premenopausal women infertile
We show for the first that NAD(P)H quinone dehydrogenase 1 (NQO1) expression is significantly increased in the endometrium of women with polycystic ovary syndrome (PCOS) and EC
We found altered expression of genes involved in insulin signalling (IGF-1, IGFBP1 and PTEN) and lipogenic gene regulation in the endometrium and serum of women with PCOS and EC compared with controls.[10,11]
Summary
Endometrial cancer (EC) is the most common gynaecological cancer affecting women in the United States, with an estimated 60 050 new cases in 2016.1 The incidence of EC has increased by over 65% since the late 1970s correlating with rising incidence of obesity and increased longevity.[2,3] EC is usually treated by hysterectomy, but surgery carries increased risk in obese women and renders premenopausal women infertile. Current hypotheses include a link between obesity and elevated oestrogen levels, inflammation, type 2 diabetes and hyperinsulinaemia.[9] In recently published studies, we found altered expression of genes involved in insulin signalling (IGF-1, IGFBP1 and PTEN) and lipogenic gene regulation in the endometrium and serum of women with PCOS and EC compared with controls.[10,11] Genes related to immunoregulation/inflammation,[12] antioxidants[9] and impaired progesterone-m ediated decidualization[13] have been suggested as possible mechanisms linking PCOS and EC.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
