Discovery and validation of peritoneal endometriosis biomarkers in peritoneal fluid and serum

Reprod Biomed Online. 2021 Oct;43(4):727-737. doi: 10.1016/j.rbmo.2021.07.002. Epub 2021 Jul 15.

Abstract

Research question: What are the potential biomarkers for peritoneal endometriosis in peritoneal fluid and serum?

Design: Case-control studies composed of independent discovery and validation sets were conducted. In the discovery set, untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, multivariable and univariable analyses were conducted to generate global metabolomic profiles of peritoneal fluid for endometriosis and to identify potential metabolites that could distinguish peritoneal endometriosis (n = 10) from controls (n = 31). The identified metabolites from the discovery set were validated in independent peritoneal fluid (n =19 peritoneal endometriosis and n = 20 controls) and serum samples (n = 16 peritoneal endometriosis and n = 19 controls) using targeted metabolomics. The area under the receiver-operating characteristics curve (AUC) analysis was used to evaluate the diagnostic performance of peritoneal endometriosis metabolites.

Results: In the discovery set, peritoneal fluid phosphatidylcholine (34:3) and phenylalanyl-isoleucine were significantly increased in peritoneal endometriosis groups compared with control groups, with AUC 0.77 (95% CI 0.61 to 0.92; P = 0.018) and AUC 0.98 (95% CI 0.95 to 1.02; P < 0.001), respectively. In the validation set, phenylalanyl-isoleucine retained discriminatory performance to distinguish peritoneal endometriosis from controls in both peritoneal fluid (AUC 0.77, 95% CI 0.61 to 0.92; P = 0.006) and serum samples (AUC 0.81, 95% CI 0.64 to 0.99; P = 0.004), with notably stronger discrimination between peritoneal endometriosis and controls in proliferative phase.

Conclusion: Our preliminary results propose phenylalanyl-isoleucine as a potential biomarker of peritoneal endometriosis, which may be used as a minimally invasive diagnostic biomarker of peritoneal endometriosis.

Keywords: Biomarker; Diagnosis; LC-MS/MS; Metabolomics; Peritoneal endometriosis.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Ascitic Fluid / metabolism*
  • Biomarkers / blood
  • Case-Control Studies
  • Endometriosis / blood*
  • Female
  • Humans
  • Metabolome
  • Metabolomics / methods
  • Peritoneal Diseases / blood*
  • Pilot Projects

Substances

  • Biomarkers