Using Affinity-Based Proteomics to Identify Diagnostic and Plasma Biomarkers for Endometriosis
Abstract
Background: Endometriosis is a condition in which the normal lining of the uterus grows in locations within the body that are outside of the uterus. These growths can cause severe pain, often coinciding with the menstrual period and consequently often perceived as normal. Endometriosis affects about 10% of reproductive-aged women in the US. Currently, endometriosis is definitively diagnosed only through surgery. In combination with normalization of symptoms, the need for surgery leads to an average delay between first symptoms and diagnosis of 7 years. This delay in diagnosis can lead to prolonged pain symptoms, decreased quality of life, poor mental health, reduced fertility, loss of productivity, and potentially an increased risk for other diseases later in life. Annual healthcare costs for endometriosis approach $22 billion per year in the US. Treatment for endometriosis commonly relies on hormonal medications and surgery; however, these treatments result in side effects, often do not cure the patient, and unfortunately do not even completely relieve pain symptoms for many endometriosis patients. Therefore, there is a critical need to identify non-surgical methods for diagnosing endometriosis (like a blood test) and monitoring disease progression as well as identifying paths to new drug therapies for endometriosis patients. To date, discovery of a blood test for endometriosis has been limited by studies that fail to use samples collected before diagnosis or take into account different endometriosis subgroups. Problem: A blood test is needed to diagnose endometriosis and monitor disease progression, so women can be diagnosed earlier and ensure that women suffering from pain, infertility, and poor quality of life receive proper treatment. Approach: To address this critical problem, we will apply the ground-breaking technology to evaluate the ability of over 1,305 different proteins in the blood to distinguish between endometriosis patients and healthy women in an effort to find a blood test that can be used to diagnose endometriosis without surgery. Additionally, among women who have already been diagnosed with endometriosis, we will assess these protein markers before and after their endometriosis surgery to help identify which women will benefit from endometriosis surgery and which ones will not. We will use data and specimens from two large studies. In the Nurses’ Health Study II, blood samples were collected and stored on more than 30,000 women who were followed over time. More than 200 developed endometriosis after their blood draw. Here we have proposed to use blood samples collected 1 to 6 years before diagnosis of endometriosis from these 200 women and measure 1,305 different markers and compared the levels of these markers in 200 women without endometriosis from the same study. By comparing these samples, we will identify markers that signal the future development of endometriosis and can be used as a blood test to detect the disease. Similarly, we will utilize banked blood samples from women who participated in the Women’s Health Study: Adolescence to Adulthood (A2A). Although the samples from this study were collected at the time of diagnosis, we have valuable detailed information on endometriosis type (color and location) as well as other valuable biomarker data (like CA125) that can be used for comparison. Finally, some women who participated in the A2A and had surgery after enrolling in the study provided blood samples before and after surgery. By comparing changes in marker levels between those who do well after surgery (improved pain symptoms and quality of life) to those who do not, we will be able to determine markers that can be used to track disease progression and response to therapy. Impact: We urgently need blood tests to diagnose endometriosis in order to get women the treatments they need more quickly after pain symptoms arise to prevent women from suffering for years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910318
Entities
People
- Kathryn L. Terry
Organizations
- Brigham and Women's Hospital
- United States Army