Organ-specific, Blood Protein Biomarkers for an Informative Diagnosis of Brain an

用于脑癌和卵巢癌信息诊断的器官特异性血液蛋白生物标志物： 快速评估、验证和临床翻译技术 抽象的。我们的第一个假设是，器官特异性分泌的生物标志物构成了每个器官中生物网络的分子指纹。这些蛋白质可以在从健康到疾病和疾病治疗的进展过程中发生变化，并提供与早期诊断、疾病分层和治疗相关的信息。 进展和治疗反应。这些标志物为脑和卵巢癌诊断提供了令人兴奋的机会。我们的第二个假设是，基于血清的蛋白质生物标志物的高度多重测量将成为一个常规的临床工具，只有当这些测量是定量的，高灵敏度和廉价的。这两个假设推动了这个项目中的生物学和技术。 我们描述了一种血液蛋白生物标志物的发现和验证途径，适用于多形性成胶质细胞瘤（GBM）和卵巢癌。该途径首先通过比较深转录组分析鉴定潜在的器官特异性血液蛋白，再加上对现存血液蛋白数据库的搜索。这些生物标志物使用应用于小鼠模型和人血清的独特质谱方法进行了预先验证。最有前途的标记物被翻译到芯片上，通过分析针刺的血液对癌症患者进行大规模验证。第四步是用更稳定但性能相同的替代品取代这些测量中最昂贵的部分（抗体）。 两种纳米技术使这种方法成为可能。它们是蛋白质点击催化捕获剂（PCC剂），其是高度模块化的、化学合成的蛋白质捕获剂，其由蛋白质靶标本身组装。PCC试剂可以表现出抗体的亲和力和选择性，但也具有（生物）化学和物理稳定性-因此允许高度多重蛋白质测定的常规使用。第二 纳米技术允许对单个、特定的蛋白质分子进行常规计数，从而将多路复用蛋白质测定的灵敏度扩展了几个数量级（从而扩展到小器官）。

Organ-specific, blood protein biomarkers for an informative diagnosis of brain and ovarian cancers: technologies for rapid evaluation, validation, and clinical translation Abstract. Our first hypothesis is that organ-specific, secreted biomarkers constitute a molecular fingerprint of the biological networks in each organ. These proteins can change during the progression from health to disease and disease treatment, and provide information relevant to early diagnosis, disease stratification and progression, and therapy response. These markers provide an exciting opportunity for brain and ovarian cancer diagnostics. Our second hypothesis is that highly multiplexed measurements of serum-based protein biomarkers will become a routine clinical tool only if those measurements are quantitative, highly sensitive, and inexpensive. These two hypotheses drive the biology and technology within this project. We describe a blood protein biomarker discovery and validation pathway, as applied to qlioblastoma multiforme (GBM) and ovarian cancer. The pathway begins with the identification of potential organ-specific blood proteins via comparative deep transcriptome analysis, coupled with a search of extant blood protein databases. These biomarkers are pre-validated using unique mass spectrometric methods applied to mouse models and human sera. The most promising markers are translated onto a chip for large scale validation on cancer patients via analysis of a pinprick of blood. The fourth step is to replace the most expensive aspect of those measurements (the antibodies) with a more stable but equal performance alternative. Two nanotechnologies enable this approach. They are protein click-catalyzed capture agents (PCC agents), which are highly modular, chemically synthesized protein capture agents that are assembled by the protein target itself. PCC agents can exhibit the affinity and selectivity of antibodies, but also (bio)chemical and physical stability - thus permitting the routine use of highly multiplexed protein assays. The second nanotechnology permits the routine counting of individual, specific protein molecules, thus extending the sensitivity of multiplexed protein assays by orders of magnitude (and thus to small organs).