Urine peptide patterns for non-invasive diagnosis of endometriosis: a preliminary prospective study.
OBJECTIVE
To detect endometriosis by urine peptide biomarkers using magnetic beads-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and to identify interesting peptides using liquid chromatography tandem mass spectrometry.


METHODS
Prospective case-control study in a university-based gynecological department and central laboratory. A total of 122 patients suffering from dysmenorrhea, pelvic pain and infertility were enrolled in the study. Urine samples were collected before laparoscopy. Urine samples were analyzed by the MALDI-TOF technique to generate peptide profiling and ClinProTools software was used to set up a diagnostic model for endometriosis. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to identify interesting peptides.


RESULTS
At laparoscopy 60 patients were diagnosed with endometriosis and 62 patients were disease-free. There were 36 different peptides expressed in endometriosis patients detected by MALDI-TOF compared with controls. We established a genetic algorithm as a diagnostic model with the combination of five peptides (m/z=1433.9, 1599.4, 2085.6, 6798.0 and 3217.2). The model showed a sensitivity of 90.9% and specificity of 92.9%. Urine from another 26 symptomatic patients before laparoscopy were randomly selected and analyzed accordingly. A genetic algorithm showed a sensitivity of 90.9% and specificity of 92.9% in predicting endometriosis before laparoscopy. We also identified two peptides not belonging to the diagnostic model as collagen precursors.


CONCLUSIONS
Patients with endometriosis have a unique cluster of peptides in urine. Peptide proteomic profiling provides a novel method for non-invasive diagnosis of endometriosis.
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Science (CAMS), Beijing, China.
L
L
Wang
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Science (CAMS), Beijing, China. Electronic address: haiyuanliu@163.com.
H Y
HY
Liu
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Science (CAMS), Beijing, China.
H H
HH
Shi
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Science (CAMS), Beijing, China.
J H
JH
Lang
Proteomic Center, Peking Union Medical College (PUMC) & CAMS, Beijing, China.
W
W
Sun
D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D004412:Dysmenorrhea / Q000209:etiology / Q000652:urine; D004715:Endometriosis / Q000150:complications / Q000175:diagnosis* / Q000652:urine; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000652:urine; D017699:Pelvic Pain / Q000209:etiology / Q000652:urine; D010455:Peptides / Q000652:urine*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D016482:Urinalysis
D015415:Biomarkers; D010455:Peptides
Diagnosis; Endometriosis; LC–MS/MS; MALDI-TOF-MS; Proteomics; Urine