A Prospective, Observational and Multicentric Study to Evaluate the Performance and Clinical Utility of EndoID ELISA Kit to Determine Circulating Synuclein Gamma (SNCG) and B-cell Lymphoma-6 (BCL6) Levels as Potential Biomarkers for Endometriosis"

Background:

Endometriosis is a benign inflammatory disease defined by the presence of endometrial glands and stroma in areas outside the uterus[1]. It is estimated to affect 5%-15% of women of reproductive age [2] and is even more prevalent among women with chronic pelvic pain and infertility [3]. Endometriotic implants may be located anywhere within the pelvis, including the ovaries, pelvic peritoneum, rectovaginal septum, uterosacral ligaments, and cul-de sac. The pathophysiology of endometriosis still remains unclear. The etiologic mechanism most widely accepted is retrograde menstruation resulting in tubal backflow of endometrial cells into the pelvis during menses [4]. Over time, these cells may adhere to peritoneal surfaces, proliferate, and progressively grow. The amount, duration, and frequency of pelvic exposure to menstrual bleeding may also determine the severity of endometriosis [5]. At present, the diagnosis of endometriosis can only be definitively made by laparoscopy and biopsy of endometrial lesions for histologic confirmation. Since these are invasive procedures and usually performed at the late stages, there is an urgent need to identify non-invasive biomarkers to effectively indicate endometriosis especially at the early stages for better clinical management.

Rational:

Many genes and proteins have been proposed as biomarkers for diagnosis and follow up of endometriosis [6, 7], but none used at the present time is sensitive and specific enough either to diagnose endometriosis nor to determine the effectiveness of treatment of endometriosis. Synuclein gamma (SNCG), a member of the synuclein family of neuronal proteins, is involved in cellular proliferation by interacting with the mitotic checkpoint kinase BubR1, and inhibiting its regulatory role on cellular proliferation [8]. During the last decade, several studies have demonstrated that SNCG is correlated with poor outcome of breast cancer, ovarian cancer, colon cancer and pancreatic cancer. Interestingly, SNCG has previously been shown to have elevated expression ranging from 5- to 53-fold in ovarian endothelial cells of endometriosis lesions compared with eutopic endometrium from the same individual [9]. Similarly, B-Cell Lymphoma 6 (BCL6) protein is encoded by the BCL6 oncogene and is a zinc finger transcription factor that regulates the transcription of signal transducer and activators of transcription (STAT)-dependent IL-4 responses of B-cells [10]. Previously, BCL6 was shown to express in the endometrial epithelial cells and B-cells in lymph node germinal centres [11,12]. In addition, over-expression of BCL6 has been reported in endometrial biopsies and has been linked to the progesterone resistance and pathogenesis of endometriosis [13]. Together, both of these proteins (SNCG and BCL6) have been linked to endometriosis. However, their diagnostic/prognostic utility by non-invasive means such as measurement in peripheral blood and menstrual fluid of patients with endometriosis remains to be investigated.

Hypothesis: