Using a combination of mass-spectrometry and aptamer array-based proteomics, we characterized the
protein features of circulating extracellular vesicles (EVs) in the context of lung (LUAD) and pancreatic ductal (PDAC)
adenocarcinomas. We profiled EVs isolated from
conditioned media of LUAD and PDAC cell lines to identify EV-associated
protein cargoes released by these
cancer cell types. Analysis of the resulting data identified LUAD and PDAC specific and pan-
adenocarcinoma EV
protein signatures. Bioinformatic analyses confirmed enrichment of
proteins annotated to vesicle-associated processes and intracellular compartments, as well as representation of
cancer hallmark functions and processes. Analysis of upstream regulator networks indicated significant enrichment of TP53, MYC, TGFB1 and KRAS-driven network effectors (p = 1.69 × 10-77-2.93 × 10-49) manifest in the
adenocarcinoma sEV
protein cargoes. We extended these findings by profiling the
proteome of EVs isolated from lung (N = 15) and pancreatic ductal (N = 6)
adenocarcinoma patient plasmas obtained at time of diagnosis, along with EVs derived from matched healthy controls (N = 21). Exploration of these proteomic data revealed abundant
protein features in the plasma EVs with capacity to distinguish LUAD and PDAC cases from controls, including features yielding higher performance in the plasma EV isolates relative to unfractionated plasmas.