Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders
Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders
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DOI：
10.1136/gutjnl-2012-302047
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发表时间：
2013-01-01
期刊：
影响因子：
24.5
通讯作者：
Lankisch, Tim O.
中科院分区：
文献类型：
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作者：
Metzger, Jochen;Negm, Ahmed A.;Lankisch, Tim O.
背景由于缺乏可靠的肿瘤标志物，尤其是原发性硬化性胆管炎(PSC)患者，胆管细胞癌(CC)的诊断和治疗往往为时已晚。作者最近介绍了胆汁蛋白质组学分析用于CC诊断。然而，胆汁收集依赖于有创的内窥镜逆行胆道造影术。方法采用毛细管电泳质谱技术，根据14例CC、13例PSC和14例良性胆道疾病患者尿液中42种多肽的分布情况，建立CC特异性多肽标志物模型。结果经横断面验证，该模型正确区分了CC患者中的35例和81例PSC和BBD患者的，曲线下面积值为0.87(95%CI为0.80~0.92，p=0.0001，灵敏度为83%，特异度为79%)。对101名正常对照的评估结果显示，特异性为86%。10例PSC以上CC患者均被正确分型。大多数序列识别的多肽是间质胶原蛋白的片段，其中一些也在血液中检测到，表明它们来自肾外。肝组织切片基质金属肽酶1免疫组织化学染色显示CC患者肝上皮细胞间质胶原酶活性增强。结论尿检有助于CC与PSC和其他BBD的鉴别，为PSC监测和CC检测提供了一种新的无创性诊断手段。
Background Diagnosis and curative treatment of cholangiocarcinoma (CC) often comes too late due to the lack of reliable tumour markers especially in patients with primary sclerosing cholangitis (PSC). The authors recently introduced bile proteomic analysis for CC diagnosis. Nevertheless, bile collection depends on invasive endoscopic retrograde cholangiography. The authors therefore evaluated urine proteomic analysis for non-invasive CC diagnosis.Methods Using capillary electrophoresis mass spectrometry the authors established a CC-specific peptide marker model based on the distribution of 42 peptides in 14 CC, 13 PSC and 14 benign biliary disorder (BBD) patients.Results In cross-sectional validation of 123 patients, the urine peptide marker model correctly classified 35 of 42 CC patients and 64 of 81 PSC and BBD patients with an area under the curve value of 0.87 (95% CI 0.80 to 0.92, p = 0.0001, 83% sensitivity, 79% specificity). Evaluation of 101 normal controls resulted in 86% specificity. All 10 patients with CC on top of PSC were correctly classified. The majority of sequence-identified peptides are fragments of interstitial collagens with some of them also detected in blood indicating their extra-renal origin. Immunostaining of liver sections for matrix metallopeptidase 1 indicated increased activity of the interstitial collagenase in liver epithelial cells of CC patients.Conclusion The urine test differentiates CC from PSC and other BBD and may provide a new diagnostic non-invasive tool for PSC surveillance and CC detection.