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: 10426776
• 负责人: Michael Birrer
• 金额: $ 8.3万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426776
• 关键词: Administrative Supplement; BRCA1 gene; BRCA2 gene; Biological Markers; Blood; Carcinoma in Situ; Cells; Cohort Studies; Detection; Diagnosis; Enrollment; Ensure; Epithelial ovarian cancer; Family history of; Genomics; High Risk Woman; Inherited; Irrigation; Lesion; Liquid substance; Malignant Neoplasms; Malignant neoplasm of ovary; Methylation; Microscopic; Mutation; Operative Surgical Procedures; Ovary; Pap smear; Pathologic; Pathway interactions; Patient Schedules; Patients; Principal Investigator; Probability; Proteins; Proteomics; Publishing; Reporting; Research; Risk; Salpingo-Oophorectomy; Sampling; Schedule; Screening for Ovarian Cancer; Serous; Site; Sodium Chloride; Specificity; Statistical Data Interpretation; TP53 gene; Technology; Tissues; Tube; Uterus; Water; Woman; base; biomarker discovery; biomarker panel; cancer diagnosis; case control; cohesion; cohort; coronavirus disease; early detection biomarkers; expectation; gene panel; genome wide methylation; malignant breast neoplasm; mutational status; peritoneal cancer; protein biomarkers; sample collection; tumor DNA

Project Summary This administrative supplement seeks support for administration of the Uterine Lavage Study by the principal investigator and a research coordinator. Since the study has become a multi-year study due to COVID and other reasons, and administrative support was only available for the first year, support is needed to maintain administration of the study in a cohesive and organized fashion. The Uterine Lavage Study (ULS) aims to elucidate the relative contributions to detection of ovarian cancer from tumor DNA in uterine lavage (UL) and in Pap smears, and protein biomarkers from blood, uterine lavage, and Pap smear fluid, using newly available detection and sample collection technologies. Six sites will enroll patients into this study into two cohorts. In the first cohort, the study will enroll 200 patients scheduled for surgery for suspected ovarian cancer. Enrolling patients prior to surgical diagnosis ensures the study will be PRoBE compliant. Up to two blood draws will be obtained preoperatively or up to 31 days prior to surgery, and a uterine lavage and Pap smear will be obtained immediately prior to surgery. The expectation is that ~50 of these patients will have pathologically confirmed ovarian cancer. In a second cohort, 50 patients with an inherited BRCA1 or BRCA2 deleterious mutation without suspected ovarian cancers who are scheduled for risk-reducing salpingo- oophorectomy (RRSO) will be enrolled. Based on published reports, it is expected that that ~5 patients will have microscopic or low volume ovarian cancer identified on SEE-FIM pathologic examination. In each cohort, the patients with a pathologic invasive epithelial ovarian cancer diagnosis will be defined as Cases and patients without any ovarian cancer, primary peritoneal cancer (PPC), or other cancer identified due to the surgery, will be defined as Controls. Other cancer groups are: (i) PPC, (ii) non- invasive serous tubal intraepithelial carcinoma (STIC) lesions, (iii) non-epithelial ovarian cancers, and (iv) non-ovarian cancers. Analytic sites will determine TP53 mutation status and 25-gene panel mutation status, targeted methylation, global methylation, and protein abundances in the uterine lavage, Pap smear biospecimens, and in blood for cases and controls. Statistical analyses will identify biomarkers which distinguish cases from controls with a high specificity, and determine the complementarity of biomarkers from each biospecimen. Such analyses will identify a classifier based on a panel of biomarkers that is likely to serve as high probability candidates for the early detection of ovarian cancer.

项目摘要 这种行政补品寻求支持对子宫灌洗研究的支持 首席研究员和研究协调员。由于该研究已成为一项多年研究 出于共同原因和其他原因，只有第一年才能提供行政支持 需要以凝聚力和有组织的方式维持研究的管理。 子宫灌洗研究（ULS）旨在阐明检测卵巢的相对贡献 从子宫灌洗中的肿瘤DNA（UL）和子宫颈抹片检查中的癌症，以及血液中的蛋白质生物标志物， 使用新可用的检测和样品收集的子宫灌洗和子宫颈抹片检查 技术。六个站点将将患者纳入这两个队列。在第一个队列中，该研究 将招募200名因涉嫌卵巢癌手术的患者。在患者之前注册 手术诊断可确保该研究符合探测。最多将获得两次抽血 术前或最多在手术前31天，将获得子宫灌洗和子宫颈抹片检查 直接在手术前。期望这些患者中有〜50位将有病理 确认的卵巢癌。在第二个队列中，有50名遗传BRCA1或BRCA2患者 有害突变没有可疑的卵巢癌，他们计划降低风险的salpingo- 将招募卵巢切除术（RRSO）。根据已发表的报告，预计约有5名患者 将在透明膜病理检查中鉴定出微观或低体积的卵巢癌。在 每个队列，都将定义患有病理性上皮卵巢癌的患者 作为病例和没有任何卵巢癌的患者，原发性腹膜癌（PPC）或其他癌症 由于手术而识别，将定义为对照。其他癌症组是：（i）PPC，（ii）非 - 浸润性浆液管内癌（ETIC）病变，（III）非上皮卵巢癌和 （iv）非卵巢癌。分析位点将确定TP53突变状态和25基因面板 子宫中的突变状态，靶向甲基化，全球甲基化和蛋白质丰度 灌洗，子宫颈抹片检查生物测量以及病例和对照的血液。统计分析将确定 将病例与具有高特异性的对照区分开的生物标志物，并确定 每种生物标志物的生物标志物的互补性。这样的分析将确定基于分类器的 在一组生物标志物上，可能是早期发现的高概率候选者 卵巢癌。