Introduction. Liver is a major source of EVs circulating in the blood, with analyses suggesting that this organ may account for up to 10% of the total circulating EV pool. However, the extent to which EVs originating from the liver reflect the functional status of this organ remains unknown. This is an important knowledge gap that underpins the potential utility of circulating liver-derived EVs as a minimally invasive liquid biopsy.
Aims. The aim of this study was to characterise the proteomic profile of EVs isolated from human liver tissue (LEV) and compare this profile to that of paired liver tissue (LH).
Methods. EVs were isolated from the extracellular matrix of human liver using our established size exclusion chromatography (SEC) protocol. Samples were analysed by untargeted mass spectrometry LCMS (DIA-MS).
Results. Untargeted LCMS analyses detected 2673 proteins in liver homogenate (LH) and 1547 (58% coverage) were also detected in livers EVs (LEV). Bioinformatic analyses demonstrated comparable representation of proteins in terms of biological functions and cellular compartments. Liver EVs also contained known markers of liver cirrhosis (36), liver failure (12) and liver toxicity (148), confirming high concordance between tissue and EVs.
Discussion. These data demonstrate that EVs isolated from the extracellular matrix of liver tissue provide robust coverage of the proteomic profile of this organ and support the broader potential for the use of circulating liver-derived EVs as a liquid biopsy for this organ.