A pilot study of discovery and validation of peritoneal endometriosis biomarkers in peritoneal fluid and serum

Objective: To identify potential serum biomarkers in women with peritoneal endometriosis (PE) by first looking at its source in the peritoneal fluid (PF). Design: Case-control pilot studies, comprising independent discovery and validation sets. Setting: KK Women′s and Children′s Hospital, Singapore. Patient(s): Women with laparoscopically confirmed PE and absence of endometriosis (control). Intervention(s): None. Main Outcome Measure(s): In the discovery set, we used untargeted liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics, multivariable and univariable analyses to generate global metabolomic profiles of PF for endometriosis and to identify potential metabolites that could distinguish PE (n=10) from controls (n=31). Using targeted metabolomics, we validated the identified metabolites in PF and sera of cases (n=16 PE) and controls (n=19). We performed the area under the receiver-operating characteristics curve (AUC) analysis to evaluate the diagnostic performance of PE metabolites. Result(s): In the discovery set, PF phosphatidylcholine (34:3) and phenylalanyl-isoleucine were significantly increased in PE than controls groups, with AUC 0.77 (95% confidence interval 0.61-0.92; p=0.018) and AUC 0.98 (0.95-1.02; p<0.001), respectively. In the validation set, phenylalanyl-isoleucine retained discriminatory performance to distinguish PE from controls in both PF (AUC 0.77; 0.61-0.92; p=0.006) and serum samples (AUC 0.81; 0.64-0.99; p=0.004). Conclusion(s): Our preliminary results propose phenylalanyl-isoleucine as a potential biomarker of PE, which may be used as a minimally-invasive diagnostic biomarker of PE.