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. 2022 May 31;14(11):2744.
doi: 10.3390/cancers14112744.

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

In Ae Kim  1 , Jae Young Hur  1   2 , Hee Joung Kim  1   3 , Wan Seop Kim  1   2 , Kye Young Lee  1   3   4
Affiliations

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

In Ae Kim et al. Cancers (Basel). .

Abstract

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.

Keywords: EGFR mutation testing; NSCLC; bronchoalveolar lavage (BAL); extracellular vesicles; liquid biopsy.

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Conflict of interest statement

K.Y.L. is a cofounder of and owns stock in Exosignal, Inc. (Seoul, Korea). All the other authors have no conflicts of interest to declare. The funder (Chong Kun Dang Pharmaceutical Corp) had no role in study design, data collection, analysis and interpretation, or the decision to submit the work for publication.

Figures

Figure 1
Figure 1
Concordance rate for EGFR genotyping among tissue biopsy, BALF liquid and plasma liquid biopsy (n = 110) (double colors mean double EGFR mutation).
Figure 2
Figure 2
Comparison of sensitivity between BALF and plasma liquid biopsy depending on metastatic tumor stage. * Indicates statistically significant difference (p < 0.05). (M0: no metastasis; M1a: intrathoracic metastasis; M1b: single extrathoracic metastasis; M1c: multiple extrathoracic metastasis).
See this image and copyright information in PMC

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