Serum exosomal microRNAs as predictive markers for EGFR mutations in non–small-cell lung cancer

Abstract

Background: Current therapeutic drugs show positive effects on non–small-cell lung cancer (NSCLC) patients with mutant epidermal growth factor receptor (EGFR) expression, whereas a lesser beneficial effect is generally noted on NSCLC patients with wild-type EGFR. Therefore, identification of new detection methods for the accurate clinical diagnosis of NSCLC is essential. Methods: In this study, tumor-derived exosomes from the plasma of EGFR mutation and wild-type NSCLC patients were isolated. Extensive exosomal miRNA profiling of EGFR mutation and wild-type NSCLC patients, in comparison with healthy individuals, was performed using miRNA-sequencing analysis. Results: The variation of exosomal miRNA expression between control group (NR) and NCSLC samples (AM and AW) was identified. 96 significantly different expressed miRNAs were identified. Of these, 39 miRNAs were upregulated and 57 were downregulated. 11 miRNAs were downregulated, and 31 miRNAs were upregulated in the miRNA expression between NR and AM. Compared with healthy donors, 54 upregulated miRNAs and 36 downregulated miRNAs were observed in samples from AW patients. 40 different expressed miRNAs were identified in AM samples, compared with AW. Ten of upregulated miRNAs are miR-260, miR-1169, miR-117, miR-15b-5p, miRNA-731, miR-342-5p, miR- 898, miR-1384, miR-56, and miR-1214. Ten of downregulated miRNAs are miR-99b-5p, miR-1116, miR-689, miR-818, miR-604, miR-72, miR-955, miR-403, miR-1228, and miR-836. Conclusion: The exosomal miR-1169 and miR-260 as potential candidates, which contain specific characteristics that can distinguish between wild-type EGFR and mutant EGFR NSCLC patients in early-stage cancers.