Proteome Characterization Center: A Genoproteomics Pipeline for Cancer Biomarkers

蛋白质组表征中心：癌症生物标志物的基因蛋白质组学管道

• 批准号: 8521193
• 负责人: DANIEL Wanyui CHAN
• 金额: $ 182.42万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-29 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8521193
• 关键词: Acetylation; Affinity; Antibodies; Autoantibodies; Benign; Bioinformatics; Biological Assay; Biological Markers; Biometry; Body Fluids; Cancer Biology; Carcinoma; Characteristics; Clinical; Clinical Chemistry; Clinical Oncology; Clinical Research; DNA Sequence Rearrangement; Data; Data Analyses; Databases; Detection; Development; Differential Diagnosis; Discrimination; Disease; Experimental Designs; Future; Gene Expression; Gene Mutation; Genes; Genomics; Goals; Human; Immune response; Instruction; Knowledge; Literature; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Mass Spectrum Analysis; Measurement; Medicine; Methods; Molecular; Mutate; Oncogenes; Outcome; Ovarian; Pathway interactions; Patient advocacy; Pelvis; Performance; Phosphorylation; Plasma; Post-Translational Protein Processing; Process; Protein Microchips; Proteins; Proteome; Proteomics; Research Personnel; Resources; Route; Sampling; Scientist; Screening for Ovarian Cancer; Selection Criteria; Source; Specimen; Surrogate Markers; Technology; The Cancer Genome Atlas; Tissues; Tumor Antigens; Work; base; candidate selection; carcinogenesis; cell transformation; clinical application; evidence base; glycosylation; high throughput technology; metrology; mortality; multidisciplinary; ovarian neoplasm; success; therapeutic target; tool; translational study; tumor

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.

描述（由申请人提供）：在本申请中，我们建议建立一个由杰出的科学家和临床医生团队组成的综合蛋白质组表征中心（PCC），以便使用基因蛋白质组学方法构建癌症生物标志物管道。该多学科团队由国际公认的临床肿瘤学、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方面的专家组成。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个非常有价值的分子途径，以确定基因和途径，可能是有用的检测，鉴别诊断，结果预测和治疗目标的癌症。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战略，以建立一个证据为基础的，蛋白质组生物标志物管道卵巢癌和其他癌症。第一步是从基因组数据中发现候选生物标志物，包括使用质谱和基于人类样本亲和力的技术的TCGA。其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，以进行验证。第二步是使用靶向测定来验证这些候选物。我们的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、灵敏、定量、多重测定。虽然本申请预期不用于进行大规模临床研究，但我们认为应明确定义这些检测试剂盒的最终临床应用和性能特征。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为成功发现和验证个性化癌症药物的生物标志物提供了最佳机会。 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和其他来源鉴定的基因组改变，该申请将专注于使用最先进的蛋白质组学技术开发临床有用的蛋白质生物标志物管道，用于个性化癌症医学。