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

项目摘要 本行政副刊寻求对子宫灌洗术研究的管理支持 首席调查员和研究协调员。因为这项研究已经成为一项为期多年的研究 由于COVID和其他原因，行政支持仅在第一年可用，支持 需要以一种有凝聚力和有组织的方式维持对研究的管理。 子宫灌洗研究(ULS)旨在阐明对检测卵巢的相对贡献 来自子宫灌洗液(UL)和巴氏涂片的肿瘤DNA，以及来自血液的蛋白质生物标记物， 子宫灌洗和巴氏涂片液，使用新的检测和样本收集 技术。六个站点将把患者纳入这项研究，分成两个队列。在第一个队列中，这项研究 将招募200名因疑似卵巢癌而接受手术的患者。在此之前招募患者 手术诊断确保了研究将是符合探头的。最多两次抽血 手术前或最多手术前31天，将进行子宫冲洗和巴氏涂片。 就在手术前。预计这些患者中将有大约50人患有病理上的 确诊为卵巢癌。在第二个队列中，50名遗传性BRCA1或BRCA2患者 没有疑似卵巢癌的有害突变，计划进行降低风险的输卵管- 将接受卵巢切除术(RRSO)。根据已公布的报告，预计~5名患者 将在SEE-FIM病理检查中发现显微镜下或低体积卵巢癌。在……里面 每个队列中，病理诊断为浸润性上皮性卵巢癌的患者将被定义 AS病例和无卵巢癌、原发性腹膜癌(PPC)或其他癌症的患者 因手术而确诊的，将其定义为对照。其他癌症组有：(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，以及 (Iv)非卵巢癌。分析位点将确定TP53突变状态和25个基因小组 子宫中的突变状态、靶向甲基化、全球甲基化和蛋白质丰度 病例和对照的灌洗、巴氏涂片、血液。统计分析将确定 具有高度特异性的区分病例和对照的生物标志物，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成为早期检测的高概率候选对象 卵巢癌。

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.