Nanoscale extracellular vesicle-derived DNA is superior to circulating cell-free DNA for mutation detection in early-stage non-small-cell lung cancer

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.

Figure 1.

Measurement and analyses of nanoscale extracellular vesicle-derived DNA (nEV-DNA) and cell-free DNA (cfDNA). (A) nEV-DNA levels and cfDNA levels in two stages (cfDNA versus EV-DNA, ***P < 0.0001; stage II cfDNA versus stage I cfDNA, ***P < 0.0001; stage II nEV-DNA versus stage I nEV-DNA, **P < 0.001). (B) The correlation between nEV-DNA levels and cfDNA levels.