Genome-wide methylation and proteomic analysis of uterine lavage and cervical swab for early detection of ovarian cancer

子宫灌洗液和宫颈拭子的全基因组甲基化和蛋白质组分析用于早期检测卵巢癌

• 批准号: 10674873
• 负责人: Abhijit Patel
• 金额: $ 92.29万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674873
• 关键词: Antibodies; Apoptosis; Biological; Blood; CA-125 Antigen; Carcinoma; Carcinoma in Situ; Cells; Cervical; Circulation; Clinical; DNA; Detection; Disease; Early Diagnosis; Epigenetic Process; Epithelial Cells; Epithelium; Event; Failure; Frequencies; Genetic Predisposition to Disease; Genomics; Goals; Greater sac of peritoneum; Growth; Health; High Risk Woman; Invasive Lesion; Irrigation; Lesion; Malignant Neoplasms; Malignant neoplasm of ovary; Mammalian Oviducts; Methylation; Microscopic; Morphology; Mutation; Necrosis; Ovarian; Ovarian Serous Adenocarcinoma; Pap smear; Patients; Performance; Pilot Projects; Population; Postmenopause; Proteomics; Protocols documentation; Research; Risk; Saline; Sampling; Screening for Ovarian Cancer; Screening procedure; Secretory Cell; Serous; Signal Transduction; Site; Source; Swab; TP53 gene; Target Populations; Testing; Time; Training; Tumor Burden; Uterine cavity; Uterus; Validation; Variant; Vision; WFDC2 gene; Woman; biomarker panel; blood-based biomarker; cancer biomarkers; cancer cell; cancer diagnosis; carcinogenesis; clinical decision support; cohort; detection method; detection test; fimbria; genome wide methylation; genome-wide; innovation; mathematical model; methylation testing; mortality; novel; programs; protein biomarkers; randomized trial; screening

Project Summary/Abstract – Overall A three-decade research program developing, optimizing, and testing an annual blood-based test for the early detection of ovarian cancer in normal risk postmenopausal women failed to show a cancer-specific mortality reduction. The likely fundamental reason for the failure is the short window of opportunity provided by a blood-based signal. The proposed BCC will seek to identify an alternative biospecimen for the source of signal which has a much greater window of time for detection in early-stage disease so that an annual testing frequency will have a high likelihood of detecting ovarian cancer during its curable stages. Due to the direct connection of the uterus to the fallopian tube, where the cell of origin resides, a uterine lavage will likely contain the earliest biological signals of the presence of ovarian cancer. Identifying a minimal ovarian cancer signal amongst a much greater background of uterine epithelium cells and cellular material requires a very sensitive test. Our BCC will build on a recently developed innovative genome-wide methylation test and combine it with a sensitive antibody based proteomic test. Having optimized the combined test to detect a signal in uterine lavage, the BCC will determine its sensitivity in Pap smears. The BCC will optimize the combined test on training uterine lavage samples, validate the test on independent validation cohort of uterine lavage samples, and assess its performance in Pap smear samples. If the optimized test is sensitive in Pap smears, then the overall goal of a clinically acceptable and readily performed test (Pap smear) conducted at a feasible frequency of every 12 months will be a crucial step towards an annual test for the early detection of ovarian cancer in normal risk postmenopausal women, the population in which 80% of ovarian cancers occur. The long-term goal is an early detection program resulting in a significant reduction in ovarian cancer mortality. The intended use of the test developed by the BCC will be as a clinical decision-support tool for screening normal risk postmenopausal women for early detection of ovarian cancer. Such a test will fill an unmet health gap since there is currently no early detection test for ovarian cancer.

项目总结/摘要——总体 一项为期三年的研究计划，开发、优化和测试针对早期疾病的年度血液测试 在正常风险绝经后妇女中检测卵巢癌未能显示癌症特异性死亡率 减少。失败的根本原因可能是企业提供的机会窗口很短。 基于血液的信号。拟议的 BCC 将寻求确定信号源的替代生物样本 它有更长的时间窗口来检测早期疾病，以便每年进行一次检测 频率将很有可能在可治愈阶段检测到卵巢癌。由于直接 子宫与输卵管的连接处，即起源细胞所在的地方，子宫灌洗可能会 含有卵巢癌存在的最早的生物信号。识别微小卵巢癌 在子宫上皮细胞和细胞物质的更大背景中发出信号需要非常 敏感测试。我们的 BCC 将建立在最近开发的创新型全基因组甲基化测试的基础上 将其与基于敏感抗体的蛋白质组测试相结合。优化组合测试以检测 子宫灌洗中的信号，BCC 将确定其在子宫颈抹片检查中的敏感性。 BCC将优化 训练子宫灌洗样本的联合测试，验证独立验证队列的测试 子宫灌洗样本，并评估其在巴氏涂片样本中的性能。如果优化测试敏感于 子宫颈抹片检查，然后进行临床可接受且易于执行的测试（子宫颈抹片检查）的总体目标 每 12 个月一次的可行频率将是迈向早期检测年度测试的关键一步 卵巢癌发生在正常风险的绝经后女性中，其中 80% 患有卵巢癌 发生。长期目标是早期检测计划，从而显着减少卵巢癌的发生 死亡。 BCC 开发的测试的预期用途将是作为临床决策支持工具 筛查正常风险的绝经后妇女以早期发现卵巢癌。这样的测试将填补 由于目前没有卵巢癌的早期检测测试，健康差距尚未得到满足。