Development of a non-invasive urine test for deep endometriosis: results from a prospective observational study.

Objective: Endometriosis affects 1 in 10 women of reproductive age worldwide, yet there is no accurate non-invasive diagnostic test that would help triage patients into the best practice treatment pathway. We aimed to identify a diagnostic biomarker for endometriosis. Study design and setting: RNA-sequence analysis of publicly available datasets was used to identify commonly dysregulated genes in endometriosis. Following, we collected urine samples from patients with symptoms of endometriosis undergoing elective laparoscopy. Patients were allocated into deep (DE), superficial (SE) or no evidence of endometriosis (symptomatic controls - SC) groups by two BSGE accredited endometriosis surgeons and a pathologist. Healthy volunteers (HV) were carefully screened and recruited. Urinary phosphoglycerate mutase 1 (PGAM1) levels were determined by enzyme-linked immunosorbent assay (ELISA) and normalised to specific gravity (SG). Population and sampling: 190 participant samples were analysed: 152 women with endometriosis, 19 SC and 19 HV. Mean age of participants was 33 (range 19-49) and body mass index (BMI) of 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). PGAM1 levels were significantly lower in participants with DE compared to SE, SC and HVs. Main outcome measures: Urinary PGAM1, as quantified using the ELISA assay, was associated with participant demographics and patient diagnosis Results and conclusions: PGAM1 is detectable in the urine of reproductive age women and can detect DE with an area under the curve (AUC) of 0.76 and a likelihood ratio (LR) of 9.8 in participants not taking hormonal medications. When participants with a preoperatively diagnosed endometrioma were excluded this rose to AUC 0.91 and LR of 17.45 making PGAM1 a promising biomarker for DE. Keywords: Endometriosis, Biomarker, Urinalysis, Diagnosis.