Berven F S, Flikka K, Berle M, Vedeler C, Ulvik R J
Institute of Medicine, University of Bergen and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.
Curr Pharm Biotechnol. 2006 Jun;7(3):147-58. doi: 10.2174/138920106777549713.
Discovery of disease specific biomarkers in human body fluids has become an important challenge in clinical proteomics. Facing the increasing threat of degenerative and disabling diseases like cancer, cardiovascular, neurological and inflammatory diseases in large parts of the world's population, there is an urgent need to improve early diagnostics. In this review we discuss possibilities and limitations connected to using mass spectrometry based proteomics in the search for novel biomarkers, with focus on multiple sclerosis as a typical representative for the large group of non-curable degenerative and disabling disease with the lack of specific tests for early diagnosis. Careful control of the pre-analytical phase including sampling, storage and fractionation of samples, in addition to a thoroughly considered patient selection, is important in order to avoid false biomarkers to appear in the resulting mass spectra. Furthermore, advanced computational tools are needed in order to discover potential biomarkers from the enormous data amounts generated by the mass spectrometers. The development of such computer tools is a research field currently in the start phase and could prove to be a bottle neck in the biomarker discovery the next years. Therefore, a rather detailed review of the most used computational and pre-analytical methods is given in this review. Mass spectrometry based biomarker discovery is undoubtedly still in its early infancy. However, in light of the potential of this technology to provide deep coverage of the body fluid proteomes, it will certainly consolidate its role in developing molecular medicine into clinical practice.
在人体体液中发现疾病特异性生物标志物已成为临床蛋白质组学中的一项重要挑战。面对全球大部分人口中癌症、心血管疾病、神经疾病和炎症性疾病等退行性和致残性疾病日益增加的威胁，迫切需要改进早期诊断方法。在本综述中，我们讨论了基于质谱的蛋白质组学在寻找新型生物标志物方面的可能性和局限性，重点关注多发性硬化症，它是一大类无法治愈的退行性和致残性疾病的典型代表，缺乏早期诊断的特异性检测方法。除了仔细考虑患者选择外，对分析前阶段进行严格控制，包括样本的采集、储存和分级分离，对于避免在所得质谱图中出现假生物标志物很重要。此外，需要先进的计算工具来从质谱仪产生的大量数据中发现潜在的生物标志物。此类计算机工具的开发目前正处于起步阶段，可能会成为未来几年生物标志物发现的瓶颈。因此，本综述对最常用的计算方法和分析前方法进行了较为详细的介绍。基于质谱的生物标志物发现无疑仍处于初期阶段。然而，鉴于该技术在深入覆盖体液蛋白质组方面具有的潜力，它必将在将分子医学发展应用于临床实践中巩固其作用。
