Proteomics of small extracellular vesicle from human plasma for hepatocellular carcinoma

Abstract Purpose Liver cancer is one of the most common tumors with the seventh-highest incidence and the third-highest mortality. Many studies have shown that small extracellular vesicles (sEVs) play an important role in liver cancer. Here, we report comprehensive signatures for sEV proteins from hepatocellular carcinoma (HCC) patient plasma, which might be valuable for the evaluation and diagnosis of HCC. Methods We extracted sEVs from the plasma of controls and HCC patients. Differentially expressed proteins in the sEVs were analyzed via label-free quantification and bioinformatic analysis. Western blotting (WB) was used to validate the abovementioned sEV proteins that differentially accumulated in the validation cohorts. Results Protein expression profiles were performed for plasma sEVs from 21 HCC patients and 15 controls. Among 335 identified proteins in our study, 27 were significantly dysregulated, including 13 increased proteins that were involved predominantly in the complement cascade (C1QB, C1QC, C4BPA, and C4BPB) and the coagulation cascade (F13B, FGA, FGB, and FGG). We verified that the protein levels of C1QB, C1QC, C4BPA, and C4BPB were increased in the plasma sEVs of HCC patients in both the discovery cohort and validation cohort. Conclusion The complement cascade in sEVs was significantly involved in HCC progression. C1QB, C1QC, C4BPA, and C4BPB were highly abundant in sEVs of HCC patients' plasma, which might be potential molecular signatures.