Extracellular Vesicle-Based Bronchoalveolar Lavage Fluid Liquid Biopsy for EGFR Mutation Testing in Advanced Non-Squamous NSCLC

• Published in: Cancers Vol. 14; no. 11; p. 2744
• Main Authors: Kim, In Ae, Hur, Jae Young, Kim, Hee Joung, Kim, Wan Seop, Lee, Kye Young
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.05.2022; MDPI
• Subjects: Alveoli; Biomarkers; Biopsy; Bronchoalveolar lavage; Bronchoscopy; Bronchus; Cancer therapies; Cell organelles; Deoxyribonucleic acid; Diagnosis; DNA; Epidermal growth factor receptors; Gene mutations; Genetic aspects; Genotyping; Health aspects; Identification and classification; Invasiveness; Kinases; Lavage; Lung cancer; Lung cancer, Non-small cell; Melting curve; Mutation; Non-small cell lung carcinoma; Physiological aspects; Plasma; Tumors; Ultracentrifugation; South Korea; United States > US; Taiwan; EGFR mutation testing; extracellular vesicles; NSCLC; liquid biopsy; bronchoalveolar lavage (BAL)
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14112744

To overcome the limitations of the tissue biopsy and plasma cfDNA liquid biopsy, we performed the EV-based BALF liquid biopsy of 224 newly diagnosed stage III-IV NSCLC patients and compared it with tissue genotyping and 110 plasma liquid biopsies. Isolation of EVs from BALF was performed by ultracentrifugation. EGFR genotyping was performed through peptide nucleic acid clamping-assisted fluorescence melting curve analysis. Compared with tissue-based genotyping, BALF liquid biopsy demonstrated a sensitivity, specificity, and concordance rates of 97.8%, 96.9%, and 97.7%, respectively. The performance of BALF liquid biopsy was almost identical to that of standard tissue-based genotyping. In contrast, plasma cfDNA-based liquid biopsy (n = 110) demonstrated sensitivity, specificity, and concordance rates of 48.5%, 86.3%, and 63.6%, respectively. The mean turn-around time of BALF liquid biopsy was significantly shorter (2.6 days) than that of tissue-based genotyping (13.9 days; p < 0.001). Therefore, the use of EV-based BALF shortens the time for confirmation of EGFR mutation status for starting EGFR-TKI treatment and can hence potentially improve clinical outcomes. As a result, we suggest that EV-based BALF EGFR testing in advanced lung NSCLC is a highly accurate rapid method and can be used as an alternative method for lung tissue biopsy.