MethylScan for Early Detection of Liver and Lung Cancer

MmethylScan 用于早期检测肝癌和肺癌

• 批准号: 10603422
• 负责人: Steven-Huy B Han
• 金额: $ 99.73万
• 依托单位: EARLYDIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603422
• 关键词: AFP gene; Address; American College of Radiology Imaging Network; Automation; Benign; Big Data; Bioinformatics; Biological Assay; Biological Markers; Biopsy; Blood; Blood specimen; CLIA certified; Cancer Detection; Cancer Patient; Case-Control Studies; Cell Differentiation process; Cirrhosis; Clinical; Clinical Research; Clinical Trials; Complement; DNA; DNA Methylation; Data; Data Analyses; Detection; Development; Devices; Early Diagnosis; Future; Goals; Gold; Hepatology; Histologic; Image; Intervention; Laboratories; Lead; Lesion; Libraries; Localized Malignant Neoplasm; Lung; Lung nodule; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of liver; Malignant neoplasm of lung; Mammalian Cell; Medicine; Methods; Methylation; Michigan; Midwestern United States; Modality; Names; Neoplasm Metastasis; Nodule; Operative Surgical Procedures; Outcome; Participant; Patients; Performance; Phase; Play; Primary carcinoma of the liver cells; Process; Prospective Studies; Radiology Specialty; Reproducibility; Research; Risk; Role; Sampling; Screening for Hepatocellular Cancer; Screening for cancer; Sensitivity and Specificity; Site; Small Business Innovation Research Grant; Specificity; TNM; Technology; Testing; Time; Tissues; Translating; Tumor Tissue; Universities; Validation; base; bisulfite sequencing; cancer diagnosis; cancer survival; cancer type; cell free DNA; clinical practice; cohort; commercialization; cost effective; detection method; high risk; imaging biomarker; improved; liquid biopsy; low dose computed tomography; lung cancer screening; machine learning algorithm; machine learning classifier; meetings; methylome; molecular marker; mortality; multidisciplinary; phase 2 study; professor; prospective; prototype; recruit; screening; tumor progression; tumorigenesis; ultrasound; validation studies

PROJECT SUMMARY The long-term goal of this SBIR Phase II project is to develop and market a commercially viable, blood-based methylation profiling test that can detect and locate multiple types of cancer early. Clinical intervention in the early stages of cancer can greatly improve the survival of cancer patients. Despite the tremendous demand for early detection methods in clinical practice, few commercial tests exist in the market. To address this unmet need, in Phase I, we developed and validated a cell-free DNA Reduced Representation Bisulfite Sequencing assay, MethylScan assay, to interrogate the methylation profile of cfDNA. The MethylScan assay was highly reproducible and reliable at low input quantities of DNA and achieved high sensitivity and specificity for detecting liver cancer. DNA methylation is established during early mammalian cell differentiation and plays an important role in the development and progression of cancer; thus, it is an ideal biomarker not only for pan-cancer detection but also for identification of tumor tissue of origin. The proposed project will translate the MethylScan assay to a surveillance product for liver cancer and expand its intended use for early lung cancer detection in patients with indeterminate lung nodules. In this Phase II study, our specific aims are as follows: Aim 1) Optimize MethylScan assay and the workflow of MethylScan Test; Aim 2) Perform a clinical validation to evaluate MethylScan test for early detection of HCC; Aim 3) Perform a clinical validation to evaluate MethylScan test for early detection of lung cancer in patients with indeterminate lung nodules. The MethylScan test will be used to perform cancer prediction in a cohort of 200 early HCC patients, 70 early lung cancer patients with malignant lung nodules, 200 patients at high risk for HCC or 50 patients with benign lung nodules. Participants in the clinical validation study will be recruited from Midwest and West Coast sites. The outcome of this project will support large clinical trials for MethylScan test as a surveillance approach for patients at risk of liver and lung cancer. The data collected will be discussed with FDA in a pre-submission meeting.

项目概要 SBIR 二期项目的长期目标是开发和销售商业上可行的基于血液的药物 甲基化分析测试可以早期检测和定位多种类型的癌症。临床干预 癌症的早期阶段可以大大提高癌症患者的生存率。尽管需求量巨大 临床实践中的早期检测方法，市场上很少有商业测试。为了解决这个未满足的问题 需要，在第一阶段，我们开发并验证了无细胞 DNA 简化表示亚硫酸氢盐测序 MmethylScan 测定，用于询问 cfDNA 的甲基化谱。 MmethylScan 检测结果高度 在低 DNA 输入量下即可重现且可靠，并实现检测的高灵敏度和特异性 肝癌。 DNA 甲基化是在早期哺乳动物细胞分化过程中建立的，在哺乳动物细胞分化过程中发挥着重要作用。 在癌症发生和进展中的作用；因此，它不仅是泛癌检测的理想生物标志物 还可用于鉴定肿瘤组织的起源。拟议的项目将把 MmethylScan 检测转化为 肝癌监测产品，并扩大其用于早期肺癌检测的预期用途 不确定的肺结节。 在这项 II 期研究中，我们的具体目标如下： 目标 1) 优化 MmethylScan 检测和工作流程 甲基扫描测试；目标 2) 进行临床验证，以评估 MmethylScan 测试对 HCC 早期检测的作用； 目标 3) 进行临床验证，以评估 MmethylScan 测试对肺癌患者早期检测的作用 不确定的肺结节。 MmethylScan 测试将用于对 200 人的队列进行癌症预测 早期HCC患者、70名患有恶性肺结节的早期肺癌患者、200名HCC高危患者 或 50 名良性肺结节患者。临床验证研究的参与者将从中西部招募 和西海岸站点。该项目的成果将支持 MmethylScan 测试的大型临床试验作为 对有肝癌和肺癌风险的患者进行监测的方法。收集的数据将与 FDA 讨论 在提交前会议上。