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.

Bioactive DNA from extracellular vesicles and particles

“…EV/EP DNA in other fluids represents additional avenues for accessing DNA biomarkers. In lung adenocarcinoma, fluid from malignant pleural effusions harboured EV DNA with EGFR mutations that reflected the tumour genotype more accurately than conventional cytology approaches 110 , 111 . A subsequent study found a broad array of tumour-derived mutations reflected in EV DNA isolated from pleural effusion supernatant 112 , further reinforcing this approach as a viable liquid biopsy option in lung cancers.…”

Tumor-Derived Exosomes in Immunosuppression and Immunotherapy

“…Exosomal DNA analysis allows the detection of tumor-specific mutations, which, in the case of heterogeneous solid tumors, can give a more accurate picture of tumor genetics overall than small tissue biopsies [46]. The presence of the mutated epidermal growth factor receptor (EGFR) alleles in exoDNA, especially mutations such as exon 19 Del and exon 21 L858R, characteristic of lung cancer cells, may be important when selecting patients for targeted therapy using a tyrosine kinase inhibitor [40,47]. It has also been shown that mtDNA present in fibroblastderived exosomes activates oxidative phosphorylation (OXPHOS) in breast cancer cells, which leads to resistance to hormone therapy in OXPHOS-dependent breast cancer [48].…”

Extracellular vesicles: novel communicators in lung diseases

“…This nucleic acid cargo may include a variety of noncoding RNAs including microRNA and long non-coding RNA (lncRNA), tRNA fragments, small-interfering RNAs, structural RNAs, small RNA transcripts and RNA-protein complexes. Other than different RNA species, exosomes also contain DNA which could represent the entire genome as well as the genomic mutations, making them excellent biomarkers [55][56][57][58]. In addition to chromosomal DNA, mitochondrial DNA has also been reported [59,60].…”