SILAC-Based Characterization of Plasma-Derived Extracellular Vesicles in Patients Undergoing Partial Hepatectomy

Post-hepatectomy liver failure (PHLF) remains a significant risk for patients undergoing partial hepatectomy (PHx). Reliable prognostic markers and treatments to enhance liver regeneration are lacking. Plasma nanoparticles, including lipoproteins, exosomes, and extracellular vesicles (EVs), can reflect systemic and tissue-wide proteostasis and stress, potentially aiding liver regeneration. Our study included nine patients with hepatocellular carcinoma (HCC) undergoing PHx. Patient plasma was collected before PHx as well as 1 and 5 days after and the EV-protein repertoire was analysed by quantitative mass spectrometry using a super-SILAC mix prepared from primary and cancer cell lines. This longitudinal proteomic analysis of the EVs circulating in the plasma of human patients undergoing PHx uncovers proteomic signatures associated with PHLF, which reflect dying hepatocytes and endothelial cells and were already present before PHx.