Y Wan1, B Liu2, H Lei3, B Zhang4, Y Wang5, H Huang4, S Chen4, Y Feng4, L Zhu5, Y Gu5, Q Zhang5, H Ma6, S-Y Zheng7. 1. Department of Biomedical Engineering, Micro and Nano Integrated Biosystem (MINIBio) Laboratory, USA; Penn State Material Research Institute, The Pennsylvania State University, University Park, USA. 2. Department of Pathology, Suzhou Municipal Hospital, Affiliate Hospital of Nanjing Medical University, Suzhou, Jiangsu, China. 3. Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; PerMed Biomedicine Institute, Shanghai, China. 4. Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. 5. PerMed Biomedicine Institute, Shanghai, China. 6. Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. Electronic address: mht7403@163.com. 7. Department of Biomedical Engineering, Micro and Nano Integrated Biosystem (MINIBio) Laboratory, USA; Penn State Material Research Institute, The Pennsylvania State University, University Park, USA; Penn State Cancer Institute, University Park, USA; Department of Electrical Engineering, The Pennsylvania State University, University Park, USA. Electronic address: sxz10@psu.edu.
Abstract
Background: The comparison between relatively intact nanoscale extracellular vesicle-derived DNA (nEV-DNA) and fragmented circulating cell-free DNA (cfDNA) in mutation detection among patients with non-small-cell lung cancer (NSCLC) has not been carried out yet, and thus deserves investigation. Patients and methods: Both nEV-DNA and cfDNA was obtained from 377 NSCLC patients with known EGFR mutation status and 69 controls. The respective EGFRE19del/T790M/L858R mutation status was interrogated with amplification-refractory-mutation-system-based PCR assays (ARMS-PCR). Results: Neither nEV-DNA nor cfDNA levels show a strong correlation with tumor volumes. There is no correlation between cfDNA and nEV-DNA levels either. The detection sensitivity of nEV-DNA and cfDNA using ARMS-PCR in early-stage NSCLC was 25.7% and 14.2%, respectively, with 96.6% and 91.7% specificity, respectively. In late-stage NSCLC, both nEV-DNA and cfDNA show ∼80% sensitivity and over 95% specificity. Conclusions: nEV-DNA is superior to cfDNA for mutation detection in early-stage NSCLC using ARMS-PCR. However, the advantages vanish in late-stage NSCLC.
Background: The comparison between relatively intact nanoscale extracellular vesicle-derived DNA (nEV-DNA) and fragmented circulating cell-free DNA (cfDNA) in mutation detection among patients with non-small-cell lung cancer (NSCLC) has not been carried out yet, and thus deserves investigation. Patients and methods: Both nEV-DNA and cfDNA was obtained from 377 NSCLCpatients with known EGFR mutation status and 69 controls. The respective EGFRE19del/T790M/L858R mutation status was interrogated with amplification-refractory-mutation-system-based PCR assays (ARMS-PCR). Results: Neither nEV-DNA nor cfDNA levels show a strong correlation with tumor volumes. There is no correlation between cfDNA and nEV-DNA levels either. The detection sensitivity of nEV-DNA and cfDNA using ARMS-PCR in early-stage NSCLC was 25.7% and 14.2%, respectively, with 96.6% and 91.7% specificity, respectively. In late-stage NSCLC, both nEV-DNA and cfDNA show ∼80% sensitivity and over 95% specificity. Conclusions: nEV-DNA is superior to cfDNA for mutation detection in early-stage NSCLC using ARMS-PCR. However, the advantages vanish in late-stage NSCLC.