Elevated exosome-derived miRNAs predict osimertinib resistance in non-small cell lung cancer

Abstract Background Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations will inevitably develop drug resistance after being treated the third-generation EGFR-tyrosine kinase inhibitor (TKI), osimertinib. Recently, information transmitted by exosomal miRNAs has attracted much attention. However, mechanism of exosome-derived in osimertinib remains unexplored. Methods We extracted and sequenced exosomes from supernatant osimertinib-resistant line, H1975-OR, sensitive H1975. The results were compared plasma exosome sequencing before appearance three NSCLC clinical oral Exosome-derived that had significantly increased expression levels screened for expanded validation other 64 patients. Results Cluster analysis target genes revealed participate mechanisms through activation bypass pathways (RAS-MAPK pathway abnormality PI3K activation). miR-184 miR-3913-5p onset resistance. Exosomal was associated TNM stage, platelet count, tumor marker carcinoembryonic antigen, distant metastases. In EGFR exon 21 L858R mutation, derived serum indicated Similarly, T790M-positive patients, level can be used as a predictive Conclusions peripheral blood could biomarkers to indicate Graphic