Clinical Proteomic Technology Assessment for Cancer

描述（由申请人提供）：在本申请中，我们提出了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，对临床癌症研究的蛋白质组技术进行比较、改进和标准化。质谱 (MS) 和相关技术的快速发展为分析蛋白质组提供了强大的新工具。最近的工作表明，蛋白质组表达的不同模式不仅表征了不同的癌症，而且还区分了反映病程和治疗反应的表型。范德比尔特 CPTAC 将实现三大目标。首先，鸟枪法蛋白质组方法将在通量和重现性方面得到提高，并在分析方法和数据分析方面实现标准化。其次，将使用稳定同位素稀释 LC-MS-MS 和反相抗体阵列技术进行有针对性的定量分析，以量化候选标记。第三，这些平台和随附的数据分析工具将标准化，以实现生物标志物发现和分析方面的实验室间合作。初步工作将采用人类癌症小鼠模型进行技术开发和验证。范德比尔特 CPTAC 项目还将收集乳腺癌、肺癌和结直肠癌患者的临床样本，这些样本将用于定义鸟枪法蛋白质组分析平台在癌症生物标志物发现和定量方面的应用。我们将与 NCI 和 CPTAC 成员合作，开发定义明确且特征全面的标准/参比材料、试剂和生物信息学工具集，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.