Biomarkers of Endometriosis

Background: Endometriosis is an under-recognised and often misdiagnosed chronic disease that affects one in ten women. It occurs when cells similar to those that line a uterus grow in other parts of the body, usually around the pelvis. The current gold standard for diagnosis of endometriosis is direct visualisation by histological analysis which can only be achieved by an invasive laparoscopy. It is estimated 176 million women and girls around the world are living with endometriosis. The condition costs $7.7 billion a year in direct medical expenses and lost productivity in Australia alone. Aim: To analyse a series of plasma samples from patients with clinically diagnosed endometriosis, others with gynaecological symptoms without endometriosis and otherwise healthy controls to identify biomarkers to differentiate these groups and potentially aid in endometriosis diagnosis. Method: A standard proteomic discovery workflow was used to search for unique biomarkers of endometriosis. Initially, pooled plasma samples from three distinct groups of patients were tested. The first group had symptoms of endometriosis with a laparoscopic/histology confirmed diagnosis. The second group also had symptoms, but the laparoscopy confirmed no endometriosis or an alternate diagnosis. The third group were healthy matched controls. The pooled plasma samples were quantitatively profiled against each other with a triplicate experiment. A validation of the biomarkers identified as significant in the discovery phase, was then undertaken in a larger clinical cohort (n=902) using a targeted multiplex mass spectrometry assay using multiple reaction monitoring (MRM). Statistical analyses were caried out using Stata and logistical regression was used to evaluate associations of biomarkers with binary clinical outcomes. Results: Out of the 943 proteins identified with [Formula: see text] 2 significant peptides in the initial discovery workflow, 47 were determined as being differential biomarkers across the three clinical groups. The derived targeted MRM assay was tested on the clinical validation cohort, and a number of candidate biomarkers were significantly associated, thereby indicating their potential for use in the diagnosis of endometriosis.