Abstract
Simple SummaryConsidering the spatiotemporal heterogeneity, more frequent monitoring of the disease progress using less-invasive liquid biopsy technologies is highly desired. Here, we demonstrate that epidermal growth factor receptor (EGFR) mutations could be readily detected from minimally invasive bronchial washing (BW)-derived EVs with good accuracy. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than in plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. We demonstrate the clinical potential of BW-derived EVs as a liquid-biopsy sample for prognosis and precision medicine in patients with lung cancer.The detection of epidermal growth factor receptor (EGFR) mutation, based on tissue biopsy samples, provides a valuable guideline for the prognosis and precision medicine in patients with lung cancer. In this study, we aimed to examine minimally invasive bronchial washing (BW)-derived extracellular vesicles (EVs) for EGFR mutation analysis in patients with lung cancer. A lab-on-a-disc equipped with a filter with 20-nm pore diameter, Exo-Disc, was used to enrich EVs in BW samples. The overall detection sensitivity of EGFR mutations in 55 BW-derived samples was 89.7% and 31.0% for EV-derived DNA (EV-DNA) and EV-excluded cell free-DNA (EV-X-cfDNA), respectively, with 100% specificity. The detection rate of T790M in 13 matched samples was 61.5%, 10.0%, and 30.8% from BW-derived EV-DNA, plasma-derived cfDNA, and tissue samples, respectively. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. The EGFR mutations can be readily detected in BW-derived EVs, which demonstrates their clinical potential as a liquid-biopsy sample that may aid precise management, including assessment of the treatment response and drug resistance in patients with lung cancer.
Highlights
Lung cancer is one of the leading causes of cancer-related deaths worldwide, with the highest cancer-related death rate [1,2,3]
Bronchial washing (BW) samples were collected from all patients and used for epidermal growth factor receptor (EGFR) mutation detection by separately isolating extracellular vesicles (EVs)-DNA and EV-X-cfDNA
EGFRmutation mutations could be readily detected from samples withthe good accuracy detection sensitivity, 26/29 (89.7%), BW-derived samples with good accuracy mutation detection sensitivity, that we achieved using BW-derived EV-derived DNA (EV-DNA) samples was slightly lower than the previous literature
Summary
Lung cancer is one of the leading causes of cancer-related deaths worldwide, with the highest cancer-related death rate [1,2,3]. Recent advances in precision medicine have had profound implications on the diagnostics and treatment monitoring in patients with lung cancer [4,5,6]. Genetic mutation of epidermal growth factor receptor (EGFR) gene is one of the critical therapeutic markers for lung cancer [10]. It is related to tyrosine kinase inhibitor (TKI)-associated drugs [11,12], which inhibit the abnormal growth of tumor by reducing the binding of tyrosine kinase with EGFR in the cancer cells. When the T790M mutation of the EGFR gene is timely detected, the resistance to the TKI drug can be overcome by selecting alterative options to improve the outcomes of patients with lung cancer [13,14,15]
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