Proteome profiling of extracellular vesicles enriched from plasma of patients with lung adenocarcinoma and malignant melanoma.

We present an optimized HiRIEF LC-MS workflow to perform an in-depth proteome profiling of plasma derived extracellular vesicles (pEVs). Here, we have applied the HiRIEF pre-fractionation and tandem mass tags (TMT)-based peptide quantification to generate pEV proteomes of 6 malignant melanoma (MM) and 6 lung adenocarcinoma (LUAD) patients. We have detected traditional EV-marker proteins, tetraspanins, ESCRTs, and several other proteins associated to EV cargo selection, trafficking/sorting, and exosome biogenesis. Importantly, we also detected many LUAD and MM related proteins in the cancer pEVs. Our advanced proteomics workflow exhibits high pEV proteome coverage and the ability to detect potential disease-specific markers in pEVs enriched from clinical plasma samples.