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炎症性肠病中的生物标志物:现状与蛋白质组学鉴定策略

Biomarkers in inflammatory bowel diseases: current status and proteomics identification strategies.

作者信息

Bennike Tue, Birkelund Svend, Stensballe Allan, Andersen Vibeke

机构信息

Tue Bennike, Svend Birkelund, Allan Stensballe, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark.

出版信息

World J Gastroenterol. 2014 Mar 28;20(12):3231-44. doi: 10.3748/wjg.v20.i12.3231.

Abstract

Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future development of preventive and treatment strategies. Thus, the clinical use of a panel of biomarkers represents a diagnostic and prognostic tool of potentially great value. The technological development in recent years within proteomic research (determination and quantification of the complete protein content) has made the discovery of novel biomarkers feasible. Several IBD-associated protein biomarkers are known, but none have been successfully implemented in daily use to distinguish CD and UC patients. The intestinal tissue remains an obvious place to search for novel biomarkers, which blood, urine or stool later can be screened for. When considering the protein complexity encountered in intestinal biopsy-samples and the recent development within the field of mass spectrometry driven quantitative proteomics, a more thorough and accurate biomarker discovery endeavor could today be performed than ever before. In this review, we report the current status of the proteomics IBD biomarkers and discuss various emerging proteomic strategies for identifying and characterizing novel biomarkers, as well as suggesting future targets for analysis.

摘要

明确诊断炎症性肠病(IBD)的两种主要形式:溃疡性结肠炎(UC)和克罗恩病(CD),在疾病早期阶段是一项挑战。诊断可能在症状出现数年后才能确立。因此,用于早期准确诊断的蛋白质生物标志物有助于临床医生改善对个体患者的治疗。此外,这些生物标志物可以帮助医生预测疾病进程,从而识别需要强化治疗的患者。疾病发作风险低的患者可以避免使用有不良事件风险的药物治疗。此外,识别疾病和病程特异性的生物标志物谱可用于确定疾病发展和治疗过程中涉及的生物学途径。总体上了解疾病机制有助于未来改进预防和治疗策略的开发。因此,一组生物标志物的临床应用代表了一种可能具有巨大价值的诊断和预后工具。近年来蛋白质组学研究(完整蛋白质含量的测定和定量)的技术发展使发现新型生物标志物成为可能。已知有几种与IBD相关的蛋白质生物标志物,但尚未有任何一种成功应用于日常临床以区分CD和UC患者。肠道组织仍然是寻找新型生物标志物的明显部位,之后可以对血液、尿液或粪便进行筛查。考虑到肠道活检样本中遇到的蛋白质复杂性以及质谱驱动的定量蛋白质组学领域的最新发展,如今可以比以往任何时候都更全面、准确地开展生物标志物发现工作。在本综述中,我们报告了蛋白质组学IBD生物标志物的现状,讨论了用于识别和表征新型生物标志物的各种新兴蛋白质组学策略,并提出了未来的分析靶点。

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