Journal
LUNG CANCER
Volume 168, Issue -, Pages 67-73Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2022.04.013
Keywords
Exhaled breath condensate (EBC); Liquid biopsy; Plasma; Mutations
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Small diagnostic tissue samples may not be sufficient to detect oncogenic driver mutations in lung cancer, while liquid biopsies may provide better reflection of tumor heterogeneity. This study found that compared to tissue NGS, both plasma and exhaled breath condensate (EBC) identified a higher number of mutations, and there were differences in mutation profiles between plasma and EBC.
Introduction: Small diagnostic tissue samples can be inadequate in testing an expanding list of validated oncogenic driver alterations and fail to reflect intratumour heterogeneity (ITGH) in lung cancer. Liquid biopsies are non-invasive and may better reflect ITGH. Most liquid biopsies are performed in the context of circulating tumour DNA (ctDNA) in plasma but Exhaled Breath Condensate (EBC) shows promise as a lung-specific liquid biopsy. Methods: In this prospective, proof-of-concept study we carried out targeted Next Generation Sequencing (NGS) on diagnostic tissue samples from 125 patients with lung cancer and compared results to plasma and EBC for 5 oncogenic driver mutations (EGFR, KRAS, PIK3CA, ERBB2, BRAF) using an ultrasensitive PCR technique (UltraSEEK T Lung Panel on the MassARRAY (R) System, Agena Bioscience, San Diego, CA, USA). Results: There was a significantly higher failure rate due to unamplifiable DNA in tissue NGS (57/125, 45.6%) compared to plasma (27/125, 21.6%, p <= 0.001 and EBC (26/125,20.8%, p = 0.001. Consequently, both plasma and EBC identified higher number of mutations compared to tissue NGS. Specifically, there were significantly higher numbers of mutations detected in EGFR, KRAS and PIK3CA in plasma (p = 9.82 x 10(-3), p = 3.14 x 10(-5), p = 1.95 x 10(-3)) and EBC (p = 2.18 x 10(-3), p = 2.28 x 10(-4),p = 0.016) compared to tissue NGS. There was considerable divergence in mutation profiles between plasma and EBC with 34/76 (44%) mutations detected in plasma and 37/74 (41.89%) in EBC unique to their respective liquid biopsy. Conclusions: The results suggest that EBC is effective in identifying clinically relevant alterations in patients with lung cancer using UltraSEEK T and has a potential role as an adjunct to plasma testing.
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