Gel-free proteomics reveals neoplastic potential in endometrium of infertile patients with stage IV ovarian endometriosis

Abstract

Background/aimsIndirect evidence suggests that eutopic endometrium of women suffering from endometriosis shows differential physiological characteristics as compared to normal endometrium in unaffected women. We have evaluated this issue by using hypothesis-neutral proteomics approach. MethodsIn order to examine the differential display of steady state expressed proteins between control endometrium from infertile women with no detectable endometriosis disease and that from infertile women with proven stage IV ovarian endometrioma, a large-scale gel-free 2D proteomic analysis, followed by QTOF LC-MS system and immunohistochemistry for subsequent validation was employed in the present study. ResultsWe could identify several dysregulated endometrial proteins in women suffering from stage IV ovarian endometriosis, which included proteins involved in regulating cellular redox states, cellular signaling, cytoskeletal functions, stress response, apoptosis, salt-water balance, and heme metabolism. Additionally, an overt indication of telomere maintenance and that of neoplastic potential of eutopic endometrium of infertile women with stage IV ovarian endometriosis was observed in post hoc bioinformatics-based analysis. This was further substantiated by consistent high immunopositive expression of four cancer-associated specific proteins (annexin A2, HSP90, PDGFRa, and Tubulin-a) in endometrium of infertile patients with stage IV ovarian endometriosis. ConclusionIt appears highly plausible that endometrial cells in women with stage IV ovarian endometriosis cannot adequately support embryo implantation process due to innate molecular inadequacies. Furthermore, these cells with molecular defects on their reflux into pelvic peritoneal niche may result in endometriotic lesion. Most importantly, pathognomonic characteristics showing marked indication of neoplastic potential in endometrium of infertile patients with stage IV ovarian endometriosis bear a possibility of inducement of oncogenic transformation especially in the high-risk population in the course of endometriosis disease progression.