Double-Stranded DNA in Exosomes of Malignant Pleural Effusions as a Novel DNA Source for EGFR Mutation Detection in Lung Adenocarcinoma

Xueling Qu

Qiuwen Li

Jingwen Yang

Huixia Zhao

Ruliang Wang+8 authors

Click here for additional data file.^{(671K, docx)}

^{Department of Oncology, The Fourth Medical Center of PLA General Hospital, Beijing, China}

^{Department of Oncology, People's Hospital of Beijing Daxing District, Capital Medical University, Beijing, China}

^{Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, China}

^{Department of Internal Medicine, Sino-Singapore Eco-City Hospital of Tianjin Medical University, Tianjin, China}

Edited by: Joshua Michael Bauml, University of Pennsylvania, United States

Reviewed by: Umberto Malapelle, University of Naples Federico II, Italy; Marzia Del Re, University of Pisa, Italy; Tejas Patil, University of Colorado Denver, United States

*Correspondence: Wenhua Xiao moc.liamtoh@oaixh_w

This article was submitted to Thoracic Oncology, a section of the journal Frontiers in Oncology

†These authors have contributed equally to this work

Edited by: Joshua Michael Bauml, University of Pennsylvania, United States

Reviewed by: Umberto Malapelle, University of Naples Federico II, Italy; Marzia Del Re, University of Pisa, Italy; Tejas Patil, University of Colorado Denver, United States

Received 2019 Jun 26; Accepted 2019 Sep 5.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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.

Keywords: exosome, double-stranded DNA, EGFR mutation, malignant pleural effusions, lung adenocarcinoma

Abstract

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.

Glossary

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.

Footnotes

Click here for additional data file.^{(671K, docx)}

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