Proteome Characterization Center: A Genoproteomics Pipeline for Cance Research

蛋白质组表征中心：癌症研究的基因蛋白质组学管道

• 批准号: 9314820
• 负责人: DANIEL Wanyui CHAN
• 金额: $ 130.77万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9314820
• 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 Alteration; Data Analyses; Databases; Detection; Development; Differential Diagnosis; Discrimination; Disease; Experimental Designs; Future; Gene Expression; 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; Ovarian; Pathway interactions; Patient advocacy; Pelvis; Performance; Phosphorylation; Plasma; Post-Translational Protein Processing; Principal Investigator; Process; Protein Microchips; Proteins; Proteome; Proteomics; Research; 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; biomarker development; biomarker discovery; cancer biomarkers; candidate marker; candidate selection; carcinogenesis; cell transformation; clinical application; early detection biomarkers; evidence base; genomic data; glycosylation; high throughput technology; metrology; mortality; multidisciplinary; outcome prediction; ovarian neoplasm; protein biomarkers; success; therapeutic target; tool; translational study; tumor

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 forthe 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 forthe discovered biomarkers. While this proposal 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 forthe success of biomarker discovery and verification for personalized cancer medicine. RELEVANCE (See instructions): Understanding the molecular networking in carcinogenesis is essential forthe development of a successful strategy to reduce cancer mortality. Based on the genomic alterations identified from TCGA and other sources, this proposal will focus on the development of a clinically useful protein biomarker pipeline using state-of-the art proteomics technologies for personalized cancer medicine.

在此应用中，我们建议建立一个集成的蛋白质组表征中心（PCC） 杰出的科学家和临床医生团队，利用构建癌症生物标志物管道 基因蛋白质组学方法。这个多学科团队由国际公认的专家组成 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/基因组学特异性 生物信息学、生物统计学和实验设计、计量/标准、技术优化、分析 施工、项目管理和患者宣传。该计划是将基因组学与蛋白质组学联系起来 （基因蛋白质组学）。我们相信基因组数据提供了一条非常有价值的分子途径 鉴定可用于检测、鉴别诊断、结果的基因和途径 癌症的预测和治疗靶点。蛋白质组学方法将提供鉴定 蛋白质固有的独特特征，包括翻译后修饰，例如糖基化 和磷酸化。我们提出了一个两步策略来构建基于证据的蛋白质组生物标志物 卵巢癌和其他癌症的管道。第一步是发现候选生物标志物 使用质谱和基于亲和力的技术对人类进行基因组数据，包括 TCGA 标本。目标是全面表征肿瘤和正常生物样本并鉴定它们的特征 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促进进展 来验证。第二步是使用靶向分析验证这些候选药物。目标是 使用优化和标准化生成准确、可重复、灵敏、定量、多重检测 已发现的生物标志物的高通量技术。虽然该提案无意进行 大规模的临床研究，我们相信最终的临床应用和性能 应明确定义这些测定的特征。凭借这个多学科的优秀团队 科学家和临床医生，我们的 PCC 为成功发现生物标志物和 个性化癌症医学的验证。 相关性（参见说明）： 了解致癌作用中的分子网络对于成功开发癌症药物至关重要 降低癌症死亡率的策略。基于 TCGA 和其他鉴定的基因组改变 消息人士称，该提案将重点关注使用以下方法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的最先进的蛋白质组学技术。

项目成果

Identification of Serological Biomarkers for Early Diagnosis of Lung Cancer Using a Protein Array-Based Approach.

• DOI: 10.1074/mcp.ra117.000212
• 发表时间: 2017-12
• 期刊: Molecular & cellular proteomics : MCP
• 作者: Pan J;Song G;Chen D;Li Y;Liu S;Hu S;Rosa C;Eichinger D;Pino I;Zhu H;Qian J;Huang Y
• 通讯作者: Huang Y

Proteogenomic analysis of human chromosome 9-encoded genes from human samples and lung cancer tissues.

• DOI: 10.1021/pr400792p
• 发表时间: 2014-01-03
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: Ahn JM;Kim MS;Kim YI;Jeong SK;Lee HJ;Lee SH;Paik YK;Pandey A;Cho JY
• 通讯作者: Cho JY

Ovarian Cancer Is an Imported Disease: Fact or Fiction?

• DOI: 10.1007/s13669-011-0004-1
• 发表时间: 2012-03
• 期刊: CURRENT OBSTETRICS AND GYNECOLOGY REPORTS
• 影响因子: 0.5
• 作者: Kuhn, Elisabetta;Kurman, Robert J;Shih, Ie-Ming
• 通讯作者: Shih, Ie-Ming

Chronic exposure to cigarette smoke leads to activation of p21 (RAC1)-activated kinase 6 (PAK6) in non-small cell lung cancer cells.

• DOI: 10.18632/oncotarget.11310
• 发表时间: 2016-09-20
• 期刊: Oncotarget
• 作者: Raja R;Sahasrabuddhe NA;Radhakrishnan A;Syed N;Solanki HS;Puttamallesh VN;Balaji SA;Nanjappa V;Datta KK;Babu N;Renuse S;Patil AH;Izumchenko E;Prasad TS;Chang X;Rangarajan A;Sidransky D;Pandey A;Gowda H;Chatterjee A
• 通讯作者: Chatterjee A

Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer.

• DOI: 10.1186/s12885-015-1855-z
• 发表时间: 2015-11-04
• 期刊: BMC cancer
• 影响因子: 3.8
• 作者: Subbannayya T;Leal-Rojas P;Barbhuiya MA;Raja R;Renuse S;Sathe G;Pinto SM;Syed N;Nanjappa V;Patil AH;Garcia P;Sahasrabuddhe NA;Nair B;Guerrero-Preston R;Navani S;Tiwari PK;Santosh V;Sidransky D;Prasad TS;Gowda H;Roa JC;Pandey A;Chatterjee A
• 通讯作者: Chatterjee A