Abstract

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. 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. The body mass indices of women with polycystic ovary syndrome (29.28±2.91kg/m2 ) and controls (28.58±2.62kg/m2 ) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22±5.70kg/m2 ). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p<0.0001). Sterol regulatory element binding protein-1 gene expression was positively correlated with body mass index (r=0.017, p=0.921) and waist-hip ratio (r=0.023, p=0.544) in polycystic ovary syndrome, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial sterol regulatory element binding protein-1 gene expression and body mass index in endometrial cancer (r=0.643, p=0.06) and waist-hip ratio (r=0.096, p=0.073). Sterol regulatory element binding protein-1 gene expression was significantly positively correlated with triglyceride in both polycystic ovary syndrome and endometrial cancer (p=0.028 and p=0.027, respectively). Quantitative serum sterol regulatory element binding protein-1 gene correlated with endometrial gene expression (p<0.05). Sterol regulatory element binding protein-1 gene expression is significantly increased in the endometrium of women with polycystic ovary syndrome and women with endometrial cancer compared with controls and positively correlates with serum triglyceride in both polycystic ovary syndrome and endometrial cancer.

Highlights

  • Women with polycystic ovary syndrome (PCOS) have a 3-fold higher risk of endometrial cancer (EC)

  • PCOS participants were recruited during their proliferative menstrual phase, histologically two women had secretory phase endometrium and eight samples were inadequate

  • This study investigates endometrial Sterol Regulatory Element Binding Protein-1 gene (SREBP1) gene expression in women with EC, PCOS and controls

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Summary

Introduction

Women with polycystic ovary syndrome (PCOS) have a 3-fold higher risk of endometrial cancer (EC). Conclusions: SREBP1 gene expression is significantly increased in the endometrium of PCOS and EC women compared with controls and positively correlates with serum triglyceride in both PCOS and EC. A recent study revealed that the expression of Silent Information Regulator-1 (SIRT1) and SREBP1 were upregulated in the endometrium of EC women compared to normal endometrium [9] This de novo lipogenesis is known to be pathognomonic in cancer cell growth [10]. Our study aimed to investigate the association between PCOS and EC by measuring endometrial SREBP1 gene expression in PCOS and EC women compared with controls. We evaluated clinical and biochemical correlations with endometrial SREBP1 gene expression levels This was considered an important additional building block to increase our understanding of the complex web of molecular interactions that increase EC risk in women with PCOS.

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