JMIR Publications

ABSTRACT

Background:

Endometrial cancer was the most common gynaecological cancer in women globally. It is getting more common with rising obesity rates and as women live longer. There is, therefore, an urgent need for research into it. However, there is uncertainty about some of the precise molecular mechanisms leading to EC. Polycystic ovary syndrome (PCOS) is the most common endocrine condition in women, and women with PCOS have a 3 to 5-fold increased risk of endometrial cancer, but the mechanisms leading to this increased risk are unclear. A pilot study in the United Kingdom, found that IGF1 gene and protein were raised in the endometrium and blood of women with EC and PCOS compared with controls. However, when we explored a publicly available database of genes (Gene Expression Omnibus), IGF-1 gene expression was higher in control compared with PCOS endometrium, in contrast to the findings from the UK study. There is, therefore, a need to investigate the crosstalk between ovaries of PCOS and the endometrium and the role played by, IGF1 in endometrial carcinogenesis.

Objective:

To compare the proliferative effects of PCOS serum on endometrial cancer cell lines with the effect of serum from women without PCOS, and IGF1 and identify differentially expressed genes and pathways activated by the various treatments.

Methods:

We intend to recruit 20 women with PCOS and 20 women without PCOS for this cross-sectional study. Endometrial cancer cell lines will be treated with serum from women with PCOS, serum from women without PCOS (controls) and IGF1, to measure cell proliferation. IGF antagonist will also be applied to serum from women without PCOS IGF1. All experiments will be carried out three times to ensure consistency. We will perform transcriptomic profiling to identify differentially expressed genes between different treatments using RNAseq. We will also perform a bioinformatic pathway analysis to identify whether any unique genes or collection of genes explain increased endometrial cancer risk in PCOS. The primary outcome measure will be the cell proliferation (growth) difference measured by cell index values during the xCELLigence real-time cell proliferation experiment.

Results:

The findings from this study will be published in high-impact journals, presented at scientific conferences, and used to inform further studies to reduce endometrial cancer rates in UAE.

Conclusions:

Investigating how IGF1 in PCOS participates in the development of EC may identify novel genetic associations between EC and PCOS. This will also facilitate future systems-biology-based pathway analysis to explore further molecular mechanisms leading to EC and will be a vital step on the road to reducing endometrial cancer in women globally.