Plasma-derived extracellular vesicle proteins as a source of biomarkers for lung adenocarcinoma

Exosomes and other extracellular vesicles (EVs) have been implicated as mediators of intercellular communication. Their release into the circulation has the potential to inform about tumor status. In-depth proteomic characterization of plasma-derived EVs has been limited by challenges in isolating EVs from protein-abundant biological fluids. We implemented a novel single-step density gradient flotation workflow for efficient and rapid isolation of highly enriched circulating EVs from plasma. Mass-spectrometry analysis of plasma EVs from subjects with lung adenocarcinoma and matched controls resulted in the identification of 640 proteins. A total of 108 proteins exhibited significant (p<0.05) differential expression in vesicle preparations derived from lung adenocarcinoma case plasmas compared to controls, of which 43 were also identified in EVs from lung adenocarcinoma cell lines. Four top performing EV-associated proteins that distinguished adenocarcinoma cases from controls, SRGN, TPM3, THBS1 and HUWE1, yielded a combined area under the receiver operating characteristic curve (AUC) of 0.90 (95% CI = 0.76-1). Our findings support the potential of EV derived proteins as a source of biomarkers that complement other approaches for tumor assessment.