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用于子宫内膜异位症无创诊断的尿液肽谱:一项初步前瞻性研究。

Urine peptide patterns for non-invasive diagnosis of endometriosis: a preliminary prospective study.

作者信息

Wang L, Liu H Y, Shi H H, Lang J H, Sun W

机构信息

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Science (CAMS), Beijing, China.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Science (CAMS), Beijing, China.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2014 Jun;177:23-8. doi: 10.1016/j.ejogrb.2014.03.011. Epub 2014 Mar 15.

DOI:10.1016/j.ejogrb.2014.03.011
PMID:24694773
Abstract

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.

STUDY DESIGN

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.

摘要

目的

利用基于磁珠的基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS)通过尿液肽生物标志物检测子宫内膜异位症,并使用液相色谱串联质谱法鉴定感兴趣的肽。

研究设计

在一所大学的妇科和中心实验室进行的前瞻性病例对照研究。共有122例患有痛经、盆腔疼痛和不孕症的患者纳入研究。在腹腔镜检查前收集尿液样本。通过MALDI-TOF技术分析尿液样本以生成肽谱,并用ClinProTools软件建立子宫内膜异位症的诊断模型。使用液相色谱串联质谱(LC-MS/MS)鉴定感兴趣的肽。

结果

在腹腔镜检查中,60例患者被诊断为子宫内膜异位症,62例患者无疾病。与对照组相比,通过MALDI-TOF检测到子宫内膜异位症患者中有36种不同的肽表达。我们建立了一种遗传算法作为诊断模型,该模型结合了五种肽(m/z = 1433.9、1599.4、2085.6、6798.0和3217.2)。该模型的灵敏度为90.9%,特异性为92.9%。随机选择另外26例有症状患者在腹腔镜检查前的尿液并进行相应分析。遗传算法在腹腔镜检查前预测子宫内膜异位症时的灵敏度为90.9%,特异性为92.9%。我们还鉴定出两种不属于诊断模型的肽为胶原前体。

结论

子宫内膜异位症患者尿液中有一组独特的肽。肽蛋白质组学分析为子宫内膜异位症的非侵入性诊断提供了一种新方法。

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