In conclusion, our results indicate that it may be interesting to further investigate the role of TAGLN, TNC and HSPG2, alongside THBS1 and CSPG4, in the context of osimertinib refractoriness in NSCLC and in particular to expand the MS profiling of EVs to a larger cohort of patients with different outcomes on osimertinib. This evidence concerns the gene HSPG2 and non-small cell lung carcinoma.