AN INFORMATIVE DIAGNOSIS OF A CANCER THROUGH MULTIPARAMETER SERUM ANALYSIS

系统生物学研究所开创的生物学和医学的系统方法 承诺在未来2-15年内改变肿瘤学的实践，将其从反应性学科 （在患者生病后响应）到预测、预防和个性化模式。在某种程度上， 通过使用血液作为健康和疾病的窗口来实现。这个观点认为生物学是由 蛋白质和其他分子的网络，在细胞内运作，通过蛋白质和其他分子的网络执行正常功能。 基因表达的调控。在疾病中，这些网络中的一个或多个受到干扰（遗传上或 环境）和基因表达模式的改变介导了疾病。这些疾病困扰 网络随着疾病的进展而动态变化，基因表达模式也是如此。 我们已经通过计算分析确定了前列腺和卵巢中的器官特异性转录本， 通过计算分析，其中一些似乎是分泌的。我们的假设是， 这些分子以可检测的水平分泌到血液中 对于蛋白质成分表达水平随着时间的推移而单独变化的每个器官， 从正常状态到疾病状态，以及从疾病状态发展到疾病状态。的威力 提出的器官特异性血液标记物的一个重要原因是，它们可以让人们专注于发生在单个器官中的变化。 器官和血液浴所有器官和组织，因此接受分泌的蛋白质指纹， 每个.因此，我们计划测试的假设，这些血指纹成为一个多参数面板， 能够识别特定疾病和这些疾病进展状态的蛋白质，并将 做了三种不同癌症的血液蛋白质组学研究：前列腺癌，卵巢癌和胶质母细胞瘤。我们 也将测试这些血液测试将允许在非常早期的阶段发现癌症的想法。需要 为了在未来将这些血液诊断技术扩展到数百万患者， 技术将不得不发展，这是最终能够使也许1000定量 蛋白质测量，快速，便宜，非常小的样品和全自动。 因此，在这项资助中，我们也将开始开发使用微流体和微流体技术的血液蛋白测量装置。 纳米技术方法将开始获得这些特征。

Abstract The systems approach to biology and medicine pioneered by the Institute for Systems Biology promises to transform the practice of oncology over the next 2-15 years moving it from a reactive discipline (responding after the patient is sick) to a predictive, preventive and personalize modes. This will be, in part, achieved by using the blood as a window into health and disease. The idea is that biology is mediated by networks of proteins and other molecules that operate within the cell to execute normal functions through the regulation of gene expression. In disease, one or more of these networks becomes perturbed (genetically or environmentally) and the altered patterns of gene expression mediate the disease. These disease-perturbed networks change dynamically with the progression of the diseases_as do their patterns of gene expression. We have identified by computational analyses organ-specific transcripts in the prostate and ovary and again by computational analyses some of these appear to be secreted. Our hypothesis is that at least some of these molecules are secreted into the blood at detectable levels and hence constitute a molecular fingerprint for each organ whose protein components change individually in their levels of expression as one shifts from the normal to a diseased state and as one progresses through the disease state. The power of these proposed organ-specific blood markers is that they let one focus on the changes that occur in just a single organ and that the blood baths all organs and tissues and hence receives secreted protein fingerprints from each. Hence we plan to test the hypothesis that these blood fingerprints become a multiparameter panel of proteins capable of identifying particular diseases and the state of progression of these diseases¿and will do using blood proteomics techniques for three different cancers: prostate, ovarian and glioblastoma. We will also test the idea that these blood tests will allow cancer to be detected at a very early stage. The need to extend these blood diagnostic techniques in the future to millions of patients means that new measuring techniques will have to be developed which are ultimately capable of making perhaps 1000 quantitative protein measurements¿and doing so rapidly, cheaply, on very small samples and fully automatically. Hence in this grant we will also begin to develop blood-protein measuring devices using microfluidic and nanotechnology approaches that will begin to acquire these features.