Decrease in the EV size in CCA versus PSC patients.HCC patients showed a slight increase in serum EV concentration compared to the other three groups.The selection of biomarkers between CCA vs. control indicated that aminopeptidase N (AMPN), pantetheinase (VNN1), and polymeric immunoglobulin receptor (PIGR) show the best diagnostic capacity.Protein levels of VNN1, C-reactive protein (CRP), FIBG, IGHA1, A1AG1, and gamma-glutamyltransferase 1 are increased in serum EV of CCA patients compared to the other groups. Here, ORM1 is linked to cholangiocarcinoma.