Proteome Characterization Center: A Genoproteomics Pipeline for Cancer Biomarkers

描述（由申请人提供）：在本次申请中，我们提议与一支优秀的科学家和临床医生团队建立一个综合蛋白质组学表征中心（PCC），以利用基因蛋白质组学方法构建癌症生物标志物管道。这个多学科团队由临床肿瘤学、临床化学、癌症生物学、蛋白质组学技术、蛋白质组学/基因组学特异性生物信息学、生物统计学和实验设计、计量学/标准、技术优化、检测构建、项目管理和患者倡导等领域的国际知名专家组成。该计划是将基因组学与蛋白质组学（genoproteomics）联系起来。我们相信基因组数据为鉴定基因和途径提供了非常有价值的分子途径，这可能对癌症的检测、鉴别诊断、结果预测和治疗靶点有用。蛋白质组学方法将提供蛋白质固有的独特特征的鉴定，包括翻译后修饰，如糖基化和磷酸化。我们提出了一个两步走的策略来构建一个基于证据的、蛋白质组学的卵巢癌和其他癌症的生物标志物管道。第一步是从基因组数据中发现候选生物标志物，包括使用质谱法和基于人类标本的亲和力技术的TCGA。目标是全面表征肿瘤和正常生物标本，并确定其蛋白质组成，以便系统地识别和优先考虑癌症相关蛋白质，以推进验证。第二步是使用靶向测定法验证这些候选药物。目标是使用优化和标准化的高通量技术为发现的生物标志物生成准确、可重复、敏感、定量、多重分析。虽然这项应用并不打算进行大规模的临床研究，但我们认为这些检测的最终临床应用和性能特征应该明确定义。凭借这支由杰出科学家和临床医生组成的多学科团队，我们的PCC为个性化癌症药物的生物标志物发现和验证的成功提供了最佳机会。

DESCRIPTION (provided by applicant): In this application, we propose to establish an integrated proteome characterization center (PCC) with an outstanding team of scientists and clinicians in order to construct a cancer biomarker pipeline using genoproteomic approaches. This multidisciplinary team consists of internationally recognized experts in clinical oncology, clinical chemistry, cancer biology, proteomic technologies, proteomics/genomics-specific bioinformatics, biostatistics and experimental design, metrology/standards, technology optimization, assay construction, project management and patient advocacy. The plan is to connect genomics with proteomics (genoproteomics). We believe that genomic data provides a highly valuable molecular route towards the identification of genes and pathways that could be useful for the detection, differential diagnosis, outcome prediction and therapeutic targets of cancer. The proteomic approaches will provide the identification of unique features that are inherent to proteins including post-translational modifications, such as glycosylation and phosphorylation. We propose a two- step strategy to construct an evidence-based, proteomic biomarker pipeline for ovarian and other carcinomas. The first step is the discovery of candidate biomarkers from genomic data including TCGA using mass spectrometry and affinity based technologies on human specimens. The goal is to comprehensively characterize tumor and normal biospecimens and identify their protein composition in order to systematically identify and prioritize cancer-related proteins for advancement to verification. The second step is the verification of these candidates using targeted assays. The goal is to generate accurate, reproducible, sensitive, quantitative, multiplex assays using optimized and standardized high-throughput technologies for the discovered biomarkers. While this application is not intended to conduct large scale clinical studies, we believe that the ultimate clinical application and the performance characteristics of these assays should be clearly defined. With this multidisciplinary team of outstanding scientists and clinicians, our PCC offers the best opportunity for the success of biomarker discovery and verification for personalized cancer medicine. RELEVANCE (See instructions): Understanding the molecular networking in carcinogenesis is essential for the development of a successful strategy to reduce cancer mortality. Based on the genomic alterations identified from TCGA and other sources, this application will focus on the development of a clinically useful protein biomarker pipeline using state-of-the art proteomics technologies for personalized cancer medicine.