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慢性胰腺炎患者胰液中蛋白质组学分析(GeLC-MS/MS)。

Proteomic analysis (GeLC-MS/MS) of ePFT-collected pancreatic fluid in chronic pancreatitis.

机构信息

Department of Pathology, Children's Hospital Boston , Boston, Massachusettes, United States.

出版信息

J Proteome Res. 2012 Mar 2;11(3):1897-912. doi: 10.1021/pr2011022. Epub 2012 Feb 7.

Abstract

Chronic pancreatitis is characterized by inflammation, fibrosis, pain, and loss of exocrine function of the pancreas. We aimed to identify differentially expressed proteins in the ePFT-collected pancreatic fluid from individuals with chronic pancreatitis (CP; n = 9) and controls with chronic abdominal pain not associated with the pancreas (NP; n = 9). Using GeLC-MS/MS techniques, we identified a total of 1391 different proteins in 18 pancreatic fluid samples. Of these proteins, 257 and 413 were identified exclusively in the control and chronic pancreatitis cohorts, respectively, and 721 were identified in both cohorts. Spectral counting and statistical analysis thereof revealed an additional 38 and 77 proteins that were up- or down-regulated, respectively, in the pancreatic fluid from individuals with chronic pancreatitis. As expected, gene ontology analysis illustrated that the largest percentage of differentially regulated proteins was secreted/extracellular in origin. In addition, proteins that were down-regulated with statistical significance in the chronic pancreatitis cohort were determined to have biological function of proteases, corresponding to the canonical pancreatic insufficiency associated with chronic pancreatitis. Proteins enriched in the pancreatic fluid of chronic pancreatitis patients had roles in fibrosis, inflammation, and pain, whereas digestive enzymes were significantly less abundant. Our workflow provided a mass spectrometry-based approach for the further study of the pancreatic fluid proteome, which may lead to the discovery potential biomarkers of chronic pancreatitis.

摘要

慢性胰腺炎的特征为胰腺炎症、纤维化、疼痛和外分泌功能丧失。我们旨在鉴定慢性胰腺炎(CP;n=9)和与胰腺无关的慢性腹痛对照者(NP;n=9)的胰液中差异表达蛋白。采用凝胶电泳-串联质谱技术,在 18 份胰液样本中共鉴定到 1391 种不同蛋白。其中,257 和 413 种蛋白分别在对照和慢性胰腺炎队列中特异表达,721 种蛋白在两个队列中均有表达。谱计数及其统计分析显示,分别有 38 和 77 种蛋白在慢性胰腺炎患者胰液中呈现上调或下调。正如预期的那样,基因本体分析表明,差异调控蛋白的最大比例来自分泌/细胞外起源。此外,在慢性胰腺炎队列中具有统计学意义的下调蛋白被确定为具有蛋白酶的生物学功能,与慢性胰腺炎相关的经典胰腺功能不全相对应。在慢性胰腺炎患者胰液中富集的蛋白在纤维化、炎症和疼痛中发挥作用,而消化酶的丰度显著降低。我们的工作流程提供了一种基于质谱的方法,用于进一步研究胰液蛋白质组,这可能会发现慢性胰腺炎的潜在生物标志物。

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