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 本行政补充申请寻求对子宫灌洗研究管理的支持， 首席研究员和研究协调员。由于这项研究已成为一项多年的研究， 由于COVID和其他原因，行政支持只在第一年提供，支持 以保持研究管理的连贯性和组织性。 子宫灌洗研究（ULS）旨在阐明卵巢癌检测的相对贡献， 来自子宫灌洗液（UL）和巴氏涂片中的肿瘤DNA的癌症，以及来自血液的蛋白质生物标志物， 子宫灌洗和巴氏涂片，使用新的检测和样本收集 技术. 6家临床试验机构将入组本研究的患者，分为两个队列。在第一个队列中， 将招募200名因疑似卵巢癌而计划手术的患者。入组患者之前 手术诊断确保研究符合PRoBE。最多将进行两次抽血 术前或手术前31天内，进行子宫灌洗和巴氏涂片检查 在手术前。预计这些患者中约有50例将出现病理性 确诊卵巢癌在第二个队列中，50名遗传性BRCA 1或BRCA 2 没有可疑卵巢癌的有害突变， 将入组卵巢切除术（RRSO）。根据已发表的报告，预计约5例患者 将在SEE-MRI病理检查中发现显微镜下或低体积卵巢癌。在 每个队列中，将定义诊断为病理性浸润性上皮性卵巢癌的患者 作为没有任何卵巢癌、原发性腹膜癌（PPC）或其他癌症的病例和患者 由于手术而识别的患者将被定义为对照组。其他癌症组是：（i）PPC，（ii）非- 浸润性浆液性输卵管上皮内癌（STIC）病变，（iii）非上皮性卵巢癌，和 (iv)非卵巢癌。分析中心将确定TP 53突变状态和25个基因组 突变状态、靶向甲基化、整体甲基化和子宫中的蛋白质丰度 灌洗，巴氏涂片生物标本，并在血液中的情况下和控制。统计分析将确定 生物标志物，其以高特异性将病例与对照区分开，并确定 来自每个生物样本的生物标志物的互补性。这样的分析将识别基于 在一组生物标志物上，这些生物标志物可能作为早期检测的高概率候选物， 卵巢癌