Proteomic analysis of peritoneal fluid identified COMP and TGFBI as new candidate biomarkers for endometriosis

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.

Antibody Arrays Identified Cycle-Dependent Plasma Biomarker Candidates of Peritoneal Endometriosis

“…So far, a number of studies have used this platform to discover novel pathways or biomarker signatures specific for certain diseases [ 32 , 33 , 34 ]. Additionally, we have previously used the same platform to successfully identify biomarker candidates for endometriosis in peritoneal fluid samples [ 26 ].…”

“…Peritoneal fluid is considered a better source for cytokine detection than peripheral blood because immune cells of peritoneal fluid specifically reflect the pathology of endometriosis [ 57 ]. In our previous study, peritoneal fluid was proven to be more appropriate for the discovery of novel biomarkers of endometriosis using antibody array platforms [ 26 ]. We were able to identify 16 differential proteins between control and endometriosis patients and successfully validated three biomarker candidates in a larger cohort.…”

“…In total, 50 µL of plasma samples was used for the analysis. Sample labeling and incubation were performed as previously described, with a few modifications [ 26 ]. Briefly, the protein concentration of plasma samples was determined using BCA assay.…”

Cartilage Oligomeric Matrix Protein, Diseases, and Therapeutic Opportunities

“…The D469del-COMP mutant mice show an increase in the adipogenic marker Cebps, possibly contributing to the imbalance between adipogenesis and osteogenesis in mutant mice [ 15 ]. Using proteomic analysis, Janša et al identified that COMP is one of the 16 proteins with different levels in peritoneal fluid of endometriosis patients compared with controls [ 136 ]. Although the cells that secrete COMP are unknown, they reported that COMP could be a potential diagnostic and predictive biomarker of endometriosis [ 136 ].…”

“…Using proteomic analysis, Janša et al identified that COMP is one of the 16 proteins with different levels in peritoneal fluid of endometriosis patients compared with controls [ 136 ]. Although the cells that secrete COMP are unknown, they reported that COMP could be a potential diagnostic and predictive biomarker of endometriosis [ 136 ].…”