Proteomics analysis of plasma for early diagnosis of endometriosis

OBJECTIVE: To test the hypothesis that differential surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein or peptide expression in plasma can be used in infertile women with or without pelvic pain to predict the presence of laparoscopically and histologically confirmed endometriosis, especially in the subpopulation with a normal preoperative gynecologic ultrasound examination. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis was performed on 254 plasma samples obtained from 89 women without endometriosis and 165 women with endometriosis (histologically confirmed) undergoing laparoscopies for infertility with or without pelvic pain. Data were analyzed using least squares support vector machines and were divided randomly (100 times) into a training data set (70%) and a test data set (30%). RESULTS: Minimal-to-mild endometriosis was best predicted (sensitivity 75%, 95% confidence interval [CI] 63–89; specificity 86%, 95% CI 71–94; positive predictive value 83.6%, negative predictive value 78.3%) using a model based on five peptide and protein peaks (range 4.898–14.698 m/z) in menstrual phase samples. Moderate-to-severe endometriosis was best predicted (sensitivity 98%, 95% CI 84–100; specificity 81%, 95% CI 67–92; positive predictive value 74.4%, negative predictive value 98.6%) using a model based on five other peptide and protein peaks (range 2.189–7.457 m/z) in luteal phase samples. The peak with the highest intensity (2.189 m/z) was identified as a fibrinogen -chain peptide. Ultrasonography-negative endometriosis was best predicted (sensitivity 88%, 95% CI 73–100; specificity 84%, 95% CI 71–96) using a model based on five peptide peaks (range 2.058–42.065 m/z) in menstrual phase samples.