Proteomic Genetic and Longitudinal Paths to Ovarian Cancer Biomarker Discovery

卵巢癌生物标志物发现的蛋白质组遗传学和纵向路径

• 批准号: 8147825
• 负责人: Michael Birrer
• 金额: $ 72.06万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-24 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8147825
• 关键词: BRCA2 Mutation; Benign; Biological Assay; Biological Markers; Blood Tests; Clinical; Conditioned Culture Media; Cyst Fluid; Detection; Disease; Family; Genetic; Genomics; High Risk Woman; Incidence; Malignant - descriptor; Malignant neoplasm of ovary; Mammalian Oviducts; Measures; Modeling; Ovarian; Ovarian Cysts; Ovarian Diseases; Ovarian Tissue; Pathogenesis; Pathway Analysis; Pathway interactions; Phenocopy; Plasma; Population; Postmenopause; Probability; Proteins; Proteomics; Recording of previous events; Screening for Ovarian Cancer; Screening procedure; Slice; Source; Specificity; Staging; System; Target Populations; Testing; Tissues; Woman; biobank; mortality

DESCRIPTION (provided by applicant): The application's broad, long-term objectives are to discover a blood test for early detection of ovarian cancer that will reduce ovarian cancer mortality through regular testing of targeted populations. Initially these populations would include women at high risk due to family history and/or presence of a BRCA1or BRCA2 mutation within the family, and all postmenopausal women where the incidence of disease is highest. The test requires high sensitivity for early stage disease and very high specificity so that few false positive tests will occur for each true positive test. The specific aims are 1) to discover high probability candidate biomarkers through proteomic analysis of biofluids from three sources a) ovarian cyst fluid from benign and malignant ovarian disease, b) conditioned media from fresh sliced washed normal and malignant tissue, and c) conditioned media from phenocopy model fallopian tube systems, 2) discover high probability candidate biomarkers from genomic analysis using Affymetrix arrays of normal fallopian tube, normal ovarian, and ovarian malignant tissue lysate filtered by a comprehensive list of secreted proteins from ovarian tissue (secretome), 3) prioritize candidate biomarkers for verification by analysis of pathways from ovarian cancer pathogenesis, 4) construct mass spectrometric assays for the top 50 candidates and measure these candidates in plasma from 100 cases and 100 benign controls, and in longitudinal plasma in cases prior to clinical detection, and in controls from an ovarian cancer screening trial, and 5) determine which candidates have earliest sensitivity by estimating the change-point (if any) at which the candidate rises significantly above baseline. The five best candidates will form a biomarker panel for further testing and refinement, outside the scope of this application, in the biorepositories of larger scale screening studies.

描述（由申请人提供）：申请的长期目标是发现早期发现卵巢癌的血液检查，该血液将通过定期测试目标人群来降低卵巢癌的死亡率。最初，这些人群将包括家族病史和/或家庭中BRCA1OR BRCA2突变的高风险的妇女，以及所有疾病发病率最高的绝经后妇女。该测试需要对早期疾病和非常高的特异性的高灵敏度，因此每次真正的阳性测试都会进行很少的假阳性测试。具体目的是1）通过对三个来源的生物流体进行蛋白质组学分析来发现高概率候选生物标志物a）来自良性和恶性卵巢疾病的卵巢囊肿液体，b）b）从新鲜切成薄片的正常和恶性组织中调节培养基，以及c）使用现象模型的替代培养基的培养基，2）替代基因型号，2）替代培养基。 normal fallopian tube, normal ovarian, and ovarian malignant tissue lysate filtered by a comprehensive list of secreted proteins from ovarian tissue (secretome), 3) prioritize candidate biomarkers for verification by analysis of pathways from ovarian cancer pathogenesis, 4) construct mass spectrometric assays for the top 50 candidates and measure these candidates in plasma from 100 cases and 100 benign controls, and in在临床检测前的病例和卵巢癌筛查试验中的对照中，纵向血浆以及5）通过估计候选者显着升高基线的变化点（如果有）来确定哪些候选者具有最早的敏感性。五个最佳候选人将在大规模筛选研究的生物库中组成一个生物标志物面板，用于在本应用程序的范围之外进行进一步的测试和精炼。