Identification of Driver Mutations and Risk Stratification in Lung Adenocarcinoma via Liquid Biopsy
Open Access
Abstract
Background: Liquid biopsy using plasma cfDNA has been established as a tool for informing the management of advanced-stage NSCLC. However, its effectiveness in early lung cancer detection, including the identification of high-risk cases, remains to be determined. Methods: We analyzed plasma cfDNA and matched tumors from 117 stage I–IV lung adenocarcinoma cases and compared the variants identified across all stages using the Oncomine Precision Assay on the GenexusTM next-generation sequencing platform. Results: Cancer-specific mutations were detected in plasma from approximately 72% (84/117) of cases (all stages), with detection rates increasing by stage. Concordance between cfDNA and tumor tissue also increased with stage 0% (stage I), 19% (stage II), 45% (stage III), and 75% (stage IV). KRAS mutations were concordant in approximately 22% (6/27) of stage II and 46% (11/24) of stage III cases. Clinically important EGFR variants showed concordance in 11% (1/9) of stage II and 80% (8/10) in stage III/IV cases. Actionable mutations, targetable with FDA-approved drugs, were detected in 11% (4/37) of stage II, 27% (12/45) of stage III, and 55% (4/9) of stage IV cases, underscoring the potential of liquid biopsy for early detection of therapeutic targets. Moreover, co-occurring mutations with varying actionability were identified more frequently in plasma than in tumor tissues. Plasma detection of clinically important KRAS and EGFR variants was mostly associated with advanced-stage disease, suggesting the presence of these variants in plasma as a potential indication of disease progression. Conclusions: Liquid biopsy holds promise for identifying high-risk lung adenocarcinoma cases and serves as a complementary diagnostic tool in advanced stages, enhancing disease management strategies.Keywords
Funding Information
- Atlantic Cancer Consortium (ACC) (E5018814, 90756293, 202005.20135.QC)
- Terry Fox Research Institute/Marathon of Hope, Dalhousie University (E5018814, 90756293, 202005.20135.QC)
- Nova Scotia Health Authority (E5018814, 90756293, 202005.20135.QC)
- Roche (Canada) (E5018814, 90756293, 202005.20135.QC)
- AstraZeneca Canada (E5018814, 90756293, 202005.20135.QC)
- EMD Serono Canada (E5018814, 90756293, 202005.20135.QC)
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