Zolg J Werner, Langen Hanno
Roche Diagnostics GmbH, Centralized Diagnostics, Nonnenwald 2, D-82377 Penzberg, Germany.
Mol Cell Proteomics. 2004 Apr;3(4):345-54. doi: 10.1074/mcp.M400007-MCP200. Epub 2004 Jan 28.
In the diagnostic and the pharmaceutical industry there is a constant need for new diagnostic markers and biomarkers with improved sensitivity and specificity. During the last 5 years, only a few novel diagnostic markers have been introduced into the market. Proteomics technologies are now offering unique chances to identify new candidate markers. Before a marker can be introduced into the market, three successive developmental phases have to be completed: the discovery phase, in which a variety of proteomics technologies are applied to identify marker candidates; the prototype developmental phase, in which immunological assays are established and validated in defined sample collectives; and finally the product development phase, with assay formats suitable for automated platforms. The hurdles that a potential candidate marker has to pass in each developmental phase before reaching the market are considerable. The costs are increasing from phase to phase, and in industry a number of questions concerning the medical need and the potential return on investment have to be answered before a proteomics discovery project is started. In this review, we will cover aspects of all three developmental phases including the repertoire of discovery tools for protein separation as well as giving an outline of modern principles of mass spectrometry for the identification of proteins.
在诊断和制药行业，一直都需要具有更高灵敏度和特异性的新型诊断标志物和生物标志物。在过去五年中，仅有少数新型诊断标志物进入市场。蛋白质组学技术如今为识别新的候选标志物提供了独特机遇。在一种标志物能够进入市场之前，必须依次完成三个连续的开发阶段：发现阶段，应用各种蛋白质组学技术来识别候选标志物；原型开发阶段，在特定样本群体中建立并验证免疫测定法；最后是产品开发阶段，采用适用于自动化平台的检测形式。一个潜在的候选标志物在进入市场之前，在每个开发阶段都必须跨越相当大的障碍。成本逐阶段增加，而且在行业中，在启动蛋白质组学发现项目之前，必须回答一些有关医疗需求和潜在投资回报的问题。在本综述中，我们将涵盖所有三个开发阶段的各个方面，包括蛋白质分离发现工具的种类，以及概述用于蛋白质鉴定的现代质谱原理。
