Challenges in uncovering non-invasive biomarkers of endometriosis

Abstract

Endometriosis affects up to 10% of women of childbearing age, causing symptoms that can include chronic pelvic pain and reduced fertility. The symptoms are not specific to the disease and can be confused with other gynecological conditions or normal menstruation. Currently, the disease can be only definitively diagnosed by laparoscopy, as no clinically accepted biomarker exists. Biomarker discovery can either follow a hypothesis-driven approach selecting targets to be tested based on current knowledge of the disease, or take an unbiased high-throughput screening “omics” approach, such as transcriptomics or proteomics, to identify markers that are unique or elevated in accessible bodily fluids of patients with the disease. Numerous studies have been conducted using these approaches to try and identify endometriosis biomarkers, but variabilities in study design, cohort selection, and analysis, together with the fact that most studies were small-scale, have made independent validation of biomarker candidates difficult. Therefore, efforts are underway to standardize cohort selection, patient data, and sample collection to allow better cross-study comparisons. Large scale multi-center studies using this standardized approach are necessary to validate existing endometriosis biomarker candidates and uncover potential new markers. Given the complexity and heterogeneity of the disease, it is likely that a panel of biomarkers will be necessary to diagnose and categorize endometriosis. Impact statement Endometriosis is a common disease affecting reproductive age women, which is associated with chronic pain and reduced fertility reducing the quality of life of many women. Definitive diagnosis requires invasive laparoscopic surgery creating a high barrier to diagnosis that can delay the onset of treatment significantly. Clinically approved biomarkers of endometriosis are currently lacking, making the discovery and validation of biomarkers that would lead to earlier diagnosis a priority for improving treatment of the disease.