Double-Stranded DNA in Exosomes of Malignant Pleural Effusions as a Novel DNA Source for EGFR Mutation Detection in Lung Adenocarcinoma
Abstract
Background: Exosomes are cell-derived vesicles and bear a specific set of nucleic acids including DNA (exoDNA). Thus, this study is to explore whether exoDNA in malignant pleural effusions (MPEs) could be a novel DNA source for mutation detection of epidermal growth factor receptor (EGFR).
Methods: In this study, 52 lung adenocarcinoma patients were enrolled, and EGFR mutation status was detected with tumor tissues as well as cell blocks and exosomes in MPEs. The sensitivity, specificity and consistency of EGFR detection using exosomes were evaluated, compared with gene detection using tumor tissues and cell blocks. And the clinical response of patients who were detected as EGFR mutation in exosomes and treated with EGFR tyrosine kinase inhibitor (EGFR-TKI) was explored.
Results: Gene detection using exosomes showed sensitivity of 100%, specificity of 96.55% and coincidence rate of 98.08% (Kappa = 0.961, P < 0.001), compared with detection using tumor tissues and cell blocks. After EGFR-TKI treatment, patients detected as EGFR mutation by exosomes showed efficacy rate of 83% and disease control rate of 100%. And patients who were detected as wild type in tumor tissues or cell blocks but EGFR mutation in exosomes turned up as PR or SD.
Conclusions: These results demonstrated that exoDNA in MPEs could be used as a DNA source for EGFR detection in lung adenocarcinoma.
Glossary
Abbreviations
EGFR | epidermal growth factor receptor |
EGFR-TKI | EGFR tyrosine kinase inhibitor |
MPEs | malignant pleural effusions |
cfDNA | cell free DNA |
exoDNA | exosomal DNA |
CR | complete remission |
PR | partial remission |
SD | stable disease |
PD | progressive disease |
exon 19 Del | deletion mutation in exon 19 |
exon 21 L858R | L858R substitute mutation in exon 21. |
Footnotes
Funding. This work was supported by National Natural Science Foundation of China (Grant No. 81372220), Natural Science Foundation of Beijing Municipality (Grant No. 7152143), Science and Technology Commission of Beijing Municipality (Grant No. D141100000214603), and PLA General Hospital (Grant No. 2015-CXYY-3042). The funding sources had no involvement in the study design, collection, analysis, or interpretation of data.
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