Novel urinary biomarkers for the non-invasive detection of endometriosis.

Introduction: Endometriosis affects 190 million women worldwide, yet there are no accurate non-invasive diagnostic tests that have been shown able to alleviate the average 8-year diagnostic delay. Phosphoglycerate mutase 1 (PGAM1) has been identified as a candidate urine biomarker and this study aims to assess its diagnostic accuracy.Methods: Patients with symptoms of endometriosis undergoing elective laparoscopy were recruited into this prospective observational study. Patients were allocated into deep (DE), superficial (SE) or symptomatic control groups (SC) by a BSGE-accredited endometriosis surgeon. Healthy volunteers (HV) were carefully screened and recruited. Urinary PGAM1 expression was determined by ELISA (Abbexa) and normalised to specific gravity.Results: 190 participant samples were analysed: 152 women with endometriosis, 19 symptomatic controls and 19 healthy volunteers. Mean age of participants was 33 (range 19-49) and BMI 27 (range 16-44). There was no difference between groups for age (p=0.15) or BMI (p=0.07). PGAM1 was detectable in every sample with a mean level of 13.8 ng/ml (range 0.25-54.22).The highest urinary PGAM1 levels were seen in HV, with significantly lower levels in women with endometriosis compared to controls (Kruskal Wallis p=0.008). In participants not taking hormonal contraception, PGAM1 levels were significantly lower in participants with DE compared to SE (Mann Whitney (MW) p=0.02), SC (MW p=0.05) and HV (MW p<0.0001). There was no association with PGAM1 levels and either age or BMI.PGAM1 can detect deep endometriosis with an AUC 0.76 and likelihood ratio (LR) of 9.8 in participants not taking hormonal medications. When participants with a pre-operatively diagnosed endometrioma were excluded this rose to AUC 0.91 and LR of 17.45 making PGAM1 a promising marker of DE.Conclusion: PGAM1 is detectable in the urine of reproductive age women and is a promising marker of DE. Further work is required to understand its clinical utility together with associations with other medical conditions, menstrual cycle and hormonal treatments.