Global Proteome Analysis of the NCI-60 Cell Line Panel, part 2

The NCI-60 cell line collection is a very widely used panel for the study of cellular mechanisms of cancer in general and in vitro drug action in particular. It is a model system for the tissue types and genetic diversity of human cancers and has been extensively molecularly characterized. Here, we present a quantitative proteome and kinome profile of the NCI-60 panel covering, in total, 10,350 proteins (including 375 protein kinases) and including a core cancer proteome of 5,578 proteins that were consistently quantified across all tissue types. Bioinformatic analysis revealed strong cell line clusters according to tissue type and disclosed hundreds of differentially regulated proteins representing potential biomarkers for numerous tumor properties. Integration with public transcriptome data showed considerable similarity between mRNA and protein expression. Modeling of proteome and drug-response profiles for 108 FDA-approved drugs identified known and potential protein markers for drug sensitivity and resistance. To enable community access to this unique resource, we incorporated it into a public database for comparative and integrative analysis (http://wzw.tum.de/proteomics/nci60).

NCI-60细胞系集是应用极为广泛的研究面板，可用于全面探究癌症的细胞机制，尤其适用于体外药物作用研究。它是模拟人类癌症组织类型与遗传多样性的经典模型系统，且已被广泛开展分子层面的表征。本研究报道了NCI-60研究面板的定量蛋白质组（proteome）与激酶组（kinome）谱，总计覆盖10350种蛋白质（其中包含375种蛋白激酶），同时包含一套在所有组织类型中均可稳定定量的核心癌症蛋白质组，涵盖5578种蛋白质。生物信息学分析揭示了基于组织类型的显著细胞系聚类结果，并发现了数百种差异调控蛋白质，这些蛋白可作为多种肿瘤特征的潜在生物标志物（biomarker）。将其与公开转录组（transcriptome）数据整合分析后，结果显示mRNA与蛋白质的表达水平具有显著相似性。针对108种经美国食品药品监督管理局（FDA）批准的药物，通过蛋白质组与药物响应谱建模分析，鉴定出了与药物敏感性及耐药性相关的已知及潜在蛋白质标志物。为便于全球科研共同体获取这一独特资源，我们将其整合至一个用于比较与整合分析的公开数据库中，数据库网址为http://wzw.tum.de/proteomics/nci60。