Proteomic, Genomic, and Longitudinal Pathways to Ovarian Cancer Biomarker Discovery

卵巢癌生物标志物发现的蛋白质组学、基因组学和纵向途径

• 批准号: 9903237
• 负责人: Michael Birrer
• 金额: $ 57.17万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903237
• 关键词: Adnexal Mass; Affect; Algorithms; BRCA1 Mutation; BRCA1 gene; BRCA2 Mutation; Benign; Biological Assay; Biological Markers; Blood; Blood Circulation; Blood Tests; Cancer Control; Cancer Detection; Cancer Patient; Clinical; Collaborations; DNA; DNA Sequence Alteration; Detection; Diagnosis; Diagnostic; Disease; Early Detection Research Network; Early Diagnosis; Family; Feces; Foundations; Genomics; High Risk Woman; High-Throughput Nucleotide Sequencing; Incidence; Label; Lead; Liquid substance; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Massive Parallel Sequencing; Measures; Mutation; Mutation Detection; Nucleic Acids; Ovary; Pathway interactions; Patients; Pelvis; Peripheral; Persons; Plasma; Plasma Proteins; Population; Population Heterogeneity; Postmenopause; Probability; Proteins; Proteomics; Recording of previous events; Research; Sampling; Screening for Ovarian Cancer; Screening for cancer; Sensitivity and Specificity; Serous; Signal Transduction; Source; Specificity; Sputum; Target Populations; Techniques; Technology; Testing; Time; Tissues; Uncertainty; Urine; Validation; Variant; Woman; age group; assay development; base; biobank; biomarker discovery; biomarker panel; cancer biomarkers; cancer cell; cancer invasiveness; candidate marker; case control; cervicovaginal; clinical application; cohort; design; genomic biomarker; improved outcome; macromolecule; mortality; next generation sequencing; novel strategies; ovarian neoplasm; pre-clinical; programs; protein biomarkers; public health relevance; screening; tumor DNA; vaginal fluid; Adnexal Mass; Affect; Algorithms; BRCA1 Mutation; BRCA1 gene; BRCA2 Mutation; Benign; Biological Assay; Biological Markers; Blood; Blood Circulation; Blood Tests; Cancer Control; Cancer Detection; Cancer Patient; Clinical; Collaborations; DNA; DNA Sequence Alteration; Detection; Diagnosis; Diagnostic; Disease; Early Detection Research Network; Early Diagnosis; Family; Feces; Foundations; Genomics; High Risk Woman; High-Throughput Nucleotide Sequencing; Incidence; Label; Lead; Liquid substance; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Massive Parallel Sequencing; Measures; Mutation; Mutation Detection; Nucleic Acids; Ovary; Pathway interactions; Patients; Pelvis; Peripheral; Persons; Plasma; Plasma Proteins; Population; Population Heterogeneity; Postmenopause; Probability; Proteins; Proteomics; Recording of previous events; Research; Sampling; Screening for Ovarian Cancer; Screening for cancer; Sensitivity and Specificity; Serous; Signal Transduction; Source; Specificity; Sputum; Target Populations; Techniques; Technology; Testing; Time; Tissues; Uncertainty; Urine; Validation; Variant; Woman; age group; assay development; base; biobank; biomarker discovery; biomarker panel; cancer biomarkers; cancer cell; cancer invasiveness; candidate marker; case control; cervicovaginal; clinical application; cohort; design; genomic biomarker; improved outcome; macromolecule; mortality; next generation sequencing; novel strategies; ovarian neoplasm; pre-clinical; programs; protein biomarkers; public health relevance; screening; tumor DNA; vaginal fluid

 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 BRCA1 or BRCA2 mutation within the family, and all postmenopausal women. This is the age group 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 longitudinal proteomic analysis of serial plasma obtained from screening studies of large cohorts, 3) prioritize candidate protein biomarkers for verification by change-point analysis and ranking by earliest change-point, 4) construct targeted mass spectrometric assays for the top 50 protein candidates and measure these candidates in longitudinal plasma in cases prior to clinical detection and in controls, where cases and controls are from an ovarian cancer screening trial, 4) determine which candidates have earliest sensitivity by estimating the change-point at which the candidate rises significantly above baseline, and 5) discover high probability candidate DNA mutational biomarkers from genomic analysis of cervico-vaginal fluid in women with malignant and benign pelvic masses, 6) validate DNA mutational candidates in an independent validation sample set of CVF from cases and benign controls. Further refinement and testing of proteomic and genomic biomarkers and their combination to identify the best panel and classifier of early detection ovarian cancer biomarkers in the biorepositories of larger scale screening studies is planned but is outside the scope of this application.

 描述（应用程序提供）：该应用程序的长期目标是发现早期检测卵巢癌的血液测试，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/或家庭中的BRCA1或BRCA2突变以及所有绝经后妇女的妇女。这是疾病事件最高的年龄组。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。 The specific aims are 1) to discover high probability candidate biomarkers through longitudinal proteomic analysis of serial plasma obtained from screening studies of large cohorts, 3) prioritize candidate protein biomarkers for verification by change-point analysis and ranking by earliest change-point, 4) construct targeted mass spectrometric assays for the top 50 protein candidates and measure these candidates in longitudinal plasma in cases prior to clinical detection and in controls, where cases and controls are from an ovarian cancer screening trial, 4) determine which candidates have early sensitivity by estimating the change-point at which the candidate rises significantly above baseline, and 5) discover high probability candidate DNA mutational biomarkers from Genomic analysis of cervico-vaginal fluid in women with malignant and benign pelvic masses, 6) validate DNA mutational candidates in an independent来自病例和良性对照的CVF的验证样本集。计划在较大规模筛查研究的生物膜上进行进一步的细化和测试，以确定早期检测卵巢癌生物标志物的最佳面板和分类器的组合，但已计划在此应用程序的范围之内。