Sunday, May 25, 2025
5/25/2025
Lung Cancer, DNA Methylation, and Liquid Biopsy - 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.
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