Multiplex analysis of 40 cytokines do not allow separation between endometriosis patients and controls

Abstract

Endometriosis is a common gynaecological condition characterized by severe pelvic pain and/or infertility. The combination of nonspecific symptoms and invasive laparoscopic diagnostics have prompted researchers to evaluate potential biomarkers that would enable a non-invasive diagnosis of endometriosis. Endometriosis is an inflammatory disease thus different cytokines represent potential diagnostic biomarkers. As panels of biomarkers are expected to enable better separation between patients and controls we evaluated 40 different cytokines in plasma samples of 210 patients (116 patients with endometriosis; 94 controls) from two medical centres (Slovenian, Austrian). Results of the univariate statistical analysis showed no differences in concentrations of the measured cytokines between patients and controls, confirmed by principal component analysis showing no clear separation amongst these two groups. In order to validate the hypothesis of a more profound (non-linear) differentiating dependency between features, machine learning methods were used. We trained four common machine learning algorithms (decision tree, linear model, k-nearest neighbour, random forest) on data from plasma levels of proteins and patients’ clinical data. The constructed models, however, did not separate patients with endometriosis from the controls with sufficient sensitivity and specificity. This study thus indicates that plasma levels of the selected cytokines have limited potential for diagnosis of endometriosis.

Peritoneal Fluid Cytokines Reveal New Insights of Endometriosis Subphenotypes

“…Notably, IFN-α2, IL-12p70, IL-18, SCGF-β, and VEGF-A are cytokines previously identified to be significantly altered between EM-from EM+ individuals [29][30][31]. However, a significant overlap between the EM-and EM+ clusters was observed (cumulative principal component (PC) score: 43%; Figure 1B), congruent with other studies [32]. We used the cumulative PC score as a measure of how well the cytokines could distinguish between EM-, EM+, EM+ Mild , and EM+ Severe patients (perfect separation of patient clusters at 100% cumulative PC score).…”

Gamma-Synuclein Levels Are Elevated in Peritoneal Fluid of Patients with Endometriosis

“…In contrast, there was no difference between the plasma SNCG levels in the patients and controls. The fact that the SNCG levels were significantly higher in the peritoneal fluid of the endometriosis patients in our study suggests that SNCG plays a role in disease formation and progression via multiple pathways, such as angiogenesis, cellular proliferation regulation, and key matrix metalloproteinase expression locally (as seen in cases of pro-inflammatory oxylipins and cytokines), without plasma level changes [3,16,25,26].…”

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

“…Biomarker discovery in the field of endometriosis has so far focused mainly on biomarkers from blood 4 , 6 , 9 , 19 – 21 . Thus, studies on peritoneal fluid biomarkers remain rare 4 , 7 , and to the best of our knowledge, to date there have not been any proteomic antibody microarray analyses of peritoneal fluid in population of women with endometriosis.…”