Abstract
Endometriosis is a common non-malignant gynecological disease that significantly compromises fertility and quality of life of the majority of patients. The gold standard for diagnosis is visual inspection of the pelvic organs by surgical laparoscopy and there are no biomarkers that would allow non-invasive diagnosis. The pathogenesis of endometriosis is not completely understood, thus analysis of peritoneal fluid might contribute in this respect. Our prospective case–control study included 58 patients undergoing laparoscopy due to infertility, 32 patients with peritoneal endometriosis (cases) and 26 patients with unexplained primary infertility (controls). Discovery proteomics using antibody microarrays that covered 1360 proteins identified 16 proteins with different levels in cases versus the control patients. The validation using an ELISA approach confirmed significant differences in the levels of cartilage oligomeric matrix protein (COMP) and transforming growth factor-β-induced protein ig-h3 (TGFBI) and nonsignificant differences in angiotensinogen (AGT). A classification model based on a linear support vector machine revealed AUC of > 0.83, sensitivity of 0.81 and specificity of 1.00. Differentially expressed proteins represent candidates for diagnostic and prognostic biomarkers or drug targets. Our findings have brought new knowledge that will be helpful in the understanding of the pathophysiology of endometriosis and warrant further studies in blood samples.
Highlights
Endometriosis is a common non-malignant gynecological disease with an estimated prevalence of 10% worldwide, which increases to 50% for women with infertility or chronic pain[1]
The antibody microarray analysis that was used in the present study identified 16 proteins that showed differences, whereby their levels were all increased in peritoneal fluid from patients with endometriosis compared to the control patients
As suggested for ovarian cancer, TGFBI might have a similar role in the development of endometriotic peritoneal implants. These significantly higher levels of TGFBI in the peritoneal fluid from women with endometriosis in the present study suggest a role for TGFBI in the pathogenesis of endometriosis
Summary
Endometriosis is a common non-malignant gynecological disease with an estimated prevalence of 10% worldwide, which increases to 50% for women with infertility or chronic pain[1]. Its pathogenesis is known to involve degradation of the extracellular matrix, aberrant apoptosis, angiogenesis, enhanced cell adhesion, cell proliferation, increased oxidative stress, inflammation processes, a disturbed immune system, and more[3,4,5,6]. As a result of these pathophysiological processes, endometrial cells survive and proliferate at ectopic sites, which can evoke chronic pelvic inflammation[7]. Ectopic endometrial cells evoke local inflammation, which is mediated by immune cells and their pro-inflammatory products[4,5,9]. Studies of peritoneal fluid might contribute to the identification of blood biomarkers for non-invasive diagnosis of endometriosis
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