MyMedR

Displaying all 7 publications

Abstract:

Sort:

Reviewing the molecular mechanisms which increase endometrial cancer (EC) risk in women with polycystic ovarian syndrome (PCOS): time for paradigm shift?

Shafiee MN, Chapman C, Barrett D, Abu J, Atiomo W

Gynecol Oncol, 2013 Nov;131(2):489-92.
PMID: 23822891 DOI: 10.1016/j.ygyno.2013.06.032

Endometrial cancer (EC) is the commonest gynaecological cancer in North American and European women. Even though it has been shown that women with polycystic ovary syndrome (PCOS) have a three-fold increase in the risk of developing EC compared to women without PCOS, the precise molecular mechanisms which increase EC risk in women with PCOS remain unclear. Clinical strategies to prevent EC in PCOS are therefore not well researched and understood. Although raised estrogen levels, hyperinsulinaemia and, reduced apoptosis have been suggested as potential mechanisms, there is a lack of clarity about how these factors and other factors may interact to increase EC risk in PCOS. This article reviews the literature, on the potential molecular links between PCOS and EC but argues for a paradigm shift, to a systems biology-based approach in future research into the molecular links between PCOS and EC. The potential challenges of a systems biology-based approach are outlined but not considered insurmountable.
Fulltext Lipidomic Biomarkers in Polycystic Ovary Syndrome and Endometrial Cancer

Shafiee MN, Ortori CA, Barrett DA, Mongan NP, Abu J, Atiomo W

Int J Mol Sci, 2020 Jul 03;21(13).
PMID: 32635401 DOI: 10.3390/ijms21134753

Women with polycystic ovary syndrome (PCOS) are more likely to develop endometrial cancer (EC). The molecular mechanisms which increase the risk of EC in PCOS are unclear. Derangements in lipid metabolism are associated with EC, but there have been no studies, investigating if this might increase the risk of EC in PCOS. This was a cross-sectional study of 102 women in three groups of 34 (PCOS, EC and controls) at Nottingham University Hospital, UK. All participants had clinical assessments, followed by obtaining plasma and endometrial tissue samples. Lipidomic analyses were performed using liquid chromatography (LC) coupled with high resolution mass spectrometry (HRMS) and the obtained lipid datasets were screened using standard software and databases. Using multivariate data analysis, there were no common markers found for EC and PCOS. However, on univariate analyses, both PCOS and EC endometrial tissue samples showed a significant decrease in monoacylglycerol 24:0 and capric acid compared to controls. Further studies are required to validate these findings and investigate the potential role of monoacylglycerol 24:0 and capric acid in the link between PCOS with EC.
Up-regulation of genes involved in the insulin signalling pathway (IGF1, PTEN and IGFBP1) in the endometrium may link polycystic ovarian syndrome and endometrial cancer

Shafiee MN, Seedhouse C, Mongan N, Chapman C, Deen S, Abu J, et al.

Mol Cell Endocrinol, 2016 Mar 15;424:94-101.
PMID: 26802879 DOI: 10.1016/j.mce.2016.01.019

Endometrial cancer (EC) is the most common gynaecological cancer amongst women in the UK. Although previous studies have found that women with polycystic ovary syndrome (PCOS) have at least a three-fold increase in endometrial cancer (EC) risk compared to women without PCOS, the precise molecular mechanisms which link between PCOS and EC remain unclear. It has been suggested that insulin resistance may contribute to the increased risk of EC in PCOS. The specific expression of genes related to the insulin-signalling pathway including the IGF system in the endometrium of women with PCOS has however never been measured and compared to that in women with EC without PCOS and control women without EC or PCOS. .

Study site: University teaching hospital in the United Kingdom
Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer

Shafiee MN, Mongan N, Seedhouse C, Chapman C, Deen S, Abu J, et al.

Acta Obstet Gynecol Scand, 2017 May;96(5):556-562.
PMID: 28176325 DOI: 10.1111/aogs.13106

INTRODUCTION: Women with polycystic ovary syndrome have a three-fold higher risk of endometrial cancer. Insulin resistance and hyperlipidemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to investigate endometrial sterol regulatory element binding protein-1 gene expression in polycystic ovary syndrome and endometrial cancer endometrium, and to correlate endometrial sterol regulatory element binding protein-1 gene expression with serum lipid profiles.
MATERIAL AND METHODS: A cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed.
RESULTS: The body mass indices of women with polycystic ovary syndrome (29.28 ± 2.91 kg/m(2) ) and controls (28.58 ± 2.62 kg/m(2) ) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 ± 5.70 kg/m(2) ). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p
Preventing endometrial cancer risk in polycystic ovarian syndrome (PCOS) women: could metformin help?

Shafiee MN, Khan G, Ariffin R, Abu J, Chapman C, Deen S, et al.

Gynecol Oncol, 2014 Jan;132(1):248-53.
PMID: 24183733 DOI: 10.1016/j.ygyno.2013.10.028

Current data indicate that there is a significant risk of endometrial cancer (EC) in women with polycystic ovarian syndrome (PCOS), although further research needed to clarify the exact molecular mechanisms. Endometrial hyperplasia is a premalignant condition that usually heralds EC and it shares identical risk factors with EC. Metabolic syndrome with a triad of obesity, hyperinsulinaemia and diabetes, which is commonly observed in PCOS appears to be a key mechanism in EC pathogenesis. Measures to improve insulin resistance could therefore play a role in reducing the risk of EC in women with PCOS. Metformin is an insulin sensitising agent which is safe, widely available and currently licensed for type-2 diabetes. It has been clearly shown in both animal and human studies that metformin is of value in reversing endometrial hyperplasia. Metformin may therefore prevent EC in PCOS. This article reviews the use of metformin in reducing EC risk in PCOS and makes a case for future research on this topic.
The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome--a proof-of-concept study

Shafiee MN, Malik DA, Yunos RI, Atiomo W, Omar MH, Ghani NA, et al.

Gynecol Endocrinol, 2015 Apr;31(4):286-90.
PMID: 25495168 DOI: 10.3109/09513590.2014.989982

The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). A total of 40 women, aged between 21 and 45 years with PCOS (Rotterdam criteria) were recruited. The participants were assessed at pre- and 3-month-post-Metformin therapy for the menstrual regularities, weight reduction, Ferriman Galway scores, fasting blood glucose (FBG), total cholesterol, LDL, HDL and p53, BCL-2 and cyclin D2 gene expression. Five participants conceived spontaneously after the initial recruitment. Majority (68%) resumed regular menstrual cycles after Metformin. There were significant reduction in BMI (p = 0.001), weight (p = 0.001) and Ferriman Galway scores (p = 0.001). A significant improvement was seen in mean FBG (p = 0.002), total cholesterol (p = 0.001), LDL (p = 0.003) and HDL cholesterol levels (p = 0.015). Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. BCL-2 and cyclin D2 (oncogenes) were slightly up-regulated without significant difference (p = 0.119 and 0.155, respectively). In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Further studies are however required to independently validate our findings.
Fulltext 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 W, Shafiee MN, Chapman C, Metzler VM, Abouzeid J, Latif A, et al.

Clin Endocrinol (Oxf), 2017 Nov;87(5):557-565.
PMID: 28748640 DOI: 10.1111/cen.13436

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