Lung Cancer, DNA Methylation, and Liquid Biopsy

肺癌、DNA 甲基化和液体活检

• 批准号: 10257798
• 负责人: Mark Anthony Nelson
• 金额: $ 39.78万
• 依托单位: PRECISION EPIGENOMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10257798
• 关键词: Aftercare; Bioinformatics; Biological Assay; Biological Markers; Biopsy Specimen; Blood; Blood specimen; CLIA certified; Cancer Detection; Cancer Patient; Cancerous; Case-Control Studies; Cells; Clinical; DNA Methylation; Data; Data Set; Development; Disease; Epigenetic Process; Excision; Future; Genes; Goals; Human; Individual; Insurance; Laboratories; Lesion; Lung nodule; Malignant Neoplasms; Malignant neoplasm of lung; Medical; Methylation; Molecular; Monitor; Multi-site clinical study; Neoplasm Metastasis; Neoplasms; Non-Small-Cell Lung Carcinoma; Normal Cell; Operative Surgical Procedures; Outcome; Patients; Peer Review; Performance; Phase; Plasma; Positioning Attribute; Process; Prognosis; Reporting; Sampling; Sensitivity and Specificity; Sentinel; Signal Transduction; Small Business Innovation Research Grant; Specificity; Specimen; Sputum; Technology; Testing; Tissues; Tumor Burden; Urine; Validation; X-Ray Computed Tomography; blood fractionation; cancer diagnosis; cancer type; case control; cell free DNA; cohort; commercialization; computed tomography screening; cost effective; diagnostic tool; disease diagnosis; epigenetic marker; epigenomics; experimental study; high risk; improved; in silico; liquid biopsy; low dose computed tomography; medically necessary care; methylation biomarker; novel; profiles in patients; prognostic tool; radiological imaging; response; routine practice; screening; treatment response; trial design; tumor

ABSTRACT Non-small cell lung cancer (NSCLC) remains a devastating disease with overall poor prognosis. Major contributing factors include obstacles to diagnosing the disease early in its course and limitations in currently available approaches to monitor therapeutic response. A liquid biopsy, or blood sample, can provide the epigenetic landscape of all cancerous lesions (primary and metastases). In addition, it offers the opportunity to systematically monitor cancer disease as the quantification of circulating cell-free DNA (cfDNA) has been shown to correlate with tumor burden. The practice of liquid biopsy as a diagnostic and prognostic tool in lung cancer patients is gradually becoming an appealing approach in the clinical routine practice, since it is noninvasive and can be easily repeated. We previously reported in silico identification of novel DNA methylation loci specifically hypermethylated in common human cancers that could be used as epigenetic biomarkers. Using a unique DNA methylation specific qPCR approach, we clinically tested a group of these cancer-specific loci on cell-free DNA (cfDNA) extracted from the plasma fraction of blood samples from healthy controls and NSCLC patients. These DNA methylation biomarkers distinguish lung cancer cases from controls with high sensitivity and specificity (AUC = 0.96). In well-defined patient cohorts, we will assess the performance of our DDX-Sentinel biomarkers to: 1) Identify cancer in indeterminate pulmonary nodules and identified by CT screening of high-risk individuals and 2) Evaluate the capability of DDX-Sentinel Biomarkers to monitor response to surgical resection. These studies will position us for a future Phase II submission.

摘要