Proteome Characterization Center: A Genoproteomics Pipeline for Cancer Biomarkers

描述(由申请人提供)：在这项申请中，我们建议建立一个整合的蛋白质组表征中心(PCC)，由一支杰出的科学家和临床医生团队组成，以利用基因蛋白质组方法构建癌症生物标记物管道。这个多学科团队由以下领域的国际知名专家组成：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/基因组学特定的生物信息学、生物统计学和实验设计、计量学/标准、技术优化、分析构建、项目管理和患者倡导。该计划是将基因组学与蛋白质组学(基因蛋白质组学)联系起来。我们认为，基因组数据提供了一条非常有价值的分子途径，可以识别有助于癌症检测、鉴别诊断、结果预测和治疗靶点的基因和途径。蛋白质组学方法将提供对蛋白质固有的独特功能的鉴定，包括翻译后修饰，如糖基化和磷酸化。我们提出了一种分两步走的策略，以构建一种基于证据的、针对卵巢癌和其他癌症的蛋白质组生物标志物管道。第一步是利用质谱学和基于人体标本的亲和力技术，从基因组数据中发现候选生物标记物，包括TCGA。目标是全面描述肿瘤和正常生物样本的特征，并确定它们的蛋白质组成，以便系统地识别和优先考虑癌症相关蛋白质，以便进入验证阶段。第二步是使用有针对性的化验对这些候选人进行核实。其目标是使用优化和标准化的高通量技术对已发现的生物标志物进行准确、可重复性、灵敏、定量和多重分析。虽然这项应用并不是为了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得到明确的定义。有了这支由杰出的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记物发现和验证提供了最好的机会。 相关性(参见说明)：了解癌症发生中的分子网络对于制定成功的降低癌症死亡率的策略至关重要。基于从TCGA和其他来源确定的基因组改变，这一应用将专注于利用最先进的蛋白质组学技术为个性化癌症药物开发临床有用的蛋白质生物标记物管道。

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.