L26/P-367 Proteomic Hallmark enrichment in eutopic endometrium of patients with minimal (ASRM I) peritoneal endometriosis

Abstract Study question Can the endometrial proteomic signature be used as a minimally invasive biomarker to detect peritoneal endometriosis in women with dysmenorrhea? Summary answer Eutopic endometrial tissue from patients with peritoneal endometriosis shows proteomic alterations relative to symptomatic controls and may therefore serve as a minimally invasive biomarker. What is known already Endometriosis is a chronic oestrogen-dependent inflammatory disease associated with dysmenorrhea and infertility. Evidence suggests that eutopic endometrium in patients undergoes biological alteration. Proteomics enables proteins to be profiled, revealing biological pathways and mapping onto hallmarks. Previous studies have reported proteomic changes linked to hallmarks such as inflammation, coagulation, and cellular stress, however, results are inconsistent across cohorts and methodologies. However there are first hints that similar findings are believed to be associated with a more extensive disease, which may then already be diagnosed by gynecological exam. Up to date, there are no biomarkers for the detection of peritoneal endometriosis only. Study design, size, duration Eutopic endometrial samples were collected after informed consent (under the ethical aproval of the local ethics committee) during laparoscopic surgery and hysteroscopy for dysmenorrhea or infertility at a university hospital between February 2019 and February 2025. Patients were divided into two groups: symptomatic controls (C, n = 10) and peritoneal endometriosis (EM, n = 10). Exclusion criteria included hormone therapy within the past 3 months, autoimmune disease, prior malignancy, psychiatric disorders, immunosuppressive therapy, or smoking history. Participants/materials, setting, methods All women had a dysmenorrhea. The endometriosis group included peritoneal lesions only (ASRM I and #ENZIAN P1O0T0), while the control group had no signs of endometriosis intraoperatively. Proteomics profiles were done by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Over-representation analysis (ORA) was applied to compare enriched endometriosis-related hallmarks between peritoneal endometriosis and symptomatic controls. Main results and the role of chance The expression of proteins varies among the group of patients with endometriosis in comparison to the symptomatic control group. ORA comparing endometriosis with symptomatic controls identified multiple significantly enriched Hallmark pathways among proteins increased in endometriosis, with the strongest enrichment observed for pathways involved in myogenesis, heme metabolism, inflammatory response and estrogen response late. Meanwhile, in symptomatic controls, ORA revealed the strongest significant enrichment of hallmark pathways related to coagulation, MYC targets and E2F targets. Limitations, reasons for caution The small sample size (n = 20) limits statistical power and generalizability. ASRM and #ENZIAN staging are operator-dependent, introducing inter-rater variability and potential misclassification. Wider implications of the findings Knowledge of the proteomic profile can facilitate understanding of the pathophysiology disease and also support the identification of a biomarker that enables non-invasive diagnosis in the early stages of the disease. Trial registration number Yes