Clinical Proteomic Technology Assessment for Cancer

描述(申请人提供)：在这份申请中，我们建议范德比尔特大学的癌症临床蛋白质组技术评估(CPTAC)计划，该计划将作为NCI CPTAC联盟的一部分，比较、改进和标准化临床癌症研究的蛋白质组技术。质谱学及其相关技术的快速发展为蛋白质组分析提供了强有力的新工具。最近的工作表明，不同的蛋白质组表达模式不仅表征了不同的癌症，而且还区分了反映疾病过程和治疗反应的表型。范德比尔特CPTAC将解决三大目标。首先，鸟枪式蛋白质组方法将在吞吐量和重复性方面得到改进，并在分析方法和数据分析方面实现标准化。其次，利用稳定同位素稀释LC-MS-MS和反相抗体阵列技术进行有针对性的定量分析，对候选标志物进行定量。第三，这些平台和附带的数据分析工具将标准化，以实现在生物标记物发现和分析方面的实验室间合作。最初的工作将使用人类癌症的小鼠模型进行技术开发和验证。Vanderbilt CPTAC计划还将收集乳腺癌、肺癌和结直肠癌患者的临床标本，这些标本将用于确定鸟枪式蛋白质组分析平台在发现和量化癌症生物标记物方面的应用。我们将与NCI和CPTAC成员合作，开发一套定义明确、特征全面的标准/参考材料、试剂和生物信息学工具，作为研究界的资源。

DESCRIPTION (provided by applicant): In this application, we propose a Clinical Proteomic Technology Assessment for Cancer (CPTAC) program at Vanderbilt University, which will work as part of the NCI CPTAC consortium to compare, improve, and standardize proteomic technologies for clinical cancer research. The rapid advance of mass spectrometry (MS) and related technologies offers powerful new tools to analyze proteomes. Recent work indicates that distinct patterns of proteome expression characterize not only different cancers but also distinguish phenotypes that reflect the course of disease and response to therapy. The Vanderbilt CPTAC will address three broad goals. First, shotgun proteome methods will be improved in both throughput and reproducibility and standardized both in analytical methods and data analysis. Second, targeted quantitative analyses by stable isotope dilution LC-MS-MS and reverse phase antibody array technology will be used to quantify candidate markers. Third, these platforms and accompanying data analysis tools will be standardized to enable interlaboratory collaborations in biomarker discovery and analysis. Initial work will employ mouse models of human cancer for technology development and validation. The Vanderbilt CPTAC program will also collect clinical specimens from patients with breast, lung, and colorectal cancers, and these specimens will be used to define the application of shotgun proteome analysis platforms to discovery and quantitation of cancer biomarkers. We will work with the NCI and members of the CPTAC to develop well defined and comprehensively characterized sets of standard/reference materials, reagents, and bioinformatics tools to serve as resources for the research community.