Non-invasive diagnosis of endometriosis and moderate-severe endometriosis with serum CA125, endocan, YKL-40, and copeptin quadruple panel

J Obstet Gynaecol. 2021 Aug;41(6):927-932. doi: 10.1080/01443615.2020.1803245. Epub 2020 Oct 16.


Considering the complex pathogenesis of endometriosis, which is associated with many cellular or molecular processes, such as proliferation, angiogenesis, inflammation, we evaluated the diagnostic value of a quadruple panel of serum markers CA125, endocan, YKL-40 and copeptin, for the prediction of endometriosis and moderate - severe endometriosis. Seventy women with endometriosis and 70 women without endometriosis were evaluated. Serum CA125, endocan, copeptin and YKL-40 levels were significantly increased in women with endometriosis compared to the women without endometriosis and in the minimal - mild endometriosis group compared to the no-endometriosis group. YKL-40, endocan and copeptin levels were significantly increased in the moderate - severe endometriosis group compared to the mild -moderate endometriosis group but the difference in CA125 levels remained non-significant. The quadruple panel score had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate - severe endometriosis. Zero or one positive marker had a sensitivity of 91.4% and specificity of 88.57% to rule out endometriosis. In conclusion, a quadruple panel of serum markers-CA125, endocan, YKL-40, and copeptin may be beneficial for the diagnosis of endometriosis and especially moderate - severe endometriosis. Further studies are needed to prove the efficacy of this panel.Impact statementWhat is already known on this subject? Many serum markers including CA125 have been investigated so far and suggested to be associated with endometriosis. However, none of these markers is sensitive and specific enough to diagnose endometriosis.What do the results of this study add? A quadruple panel score (CA125, endocan, YKL-4 and copeptin) had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate - severe endometriosis.What are the implications of these findings for clinical practice and/or further research? A high score may be beneficial to warn the surgeon about the risk of moderate to severe endometriosis if the patient will be operated anyway. A negative test of the quadruple panel may show high odds that there is no endometriosis which may prevent unnecessary surgery.

Keywords: Endometriosis; panel test; prediction; serum marker.

MeSH terms

  • Adolescent
  • Adult
  • Area Under Curve
  • Biological Specimen Banks
  • Biomarkers / blood
  • CA-125 Antigen / blood*
  • Chitinase-3-Like Protein 1 / blood*
  • Endometriosis / diagnosis*
  • Female
  • Glycopeptides / blood*
  • Hematologic Tests / statistics & numerical data*
  • Humans
  • Membrane Proteins / blood*
  • Middle Aged
  • Neoplasm Proteins / blood*
  • Predictive Value of Tests
  • Proteoglycans / blood*
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Young Adult


  • Biomarkers
  • CA-125 Antigen
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • ESM1 protein, human
  • Glycopeptides
  • MUC16 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Proteoglycans
  • copeptins