Discovery of small extracellular vesicle proteins from human serum for liver cirrhosis and liver cancer.

Abstract Hepatocellular carcinoma (HCC) is a common neoplastic transformation of the hepatocytes, which has high morbidity and mortality worldwide, particularly in Eastern Asia. HCC is also developed as a consequence of chronic liver cirrhosis, and both diseases are difficult to diagnosis and differentiate. Accurate noninvasive biomarkers for HCC and cirrhosis are urgently needed. In the search for novel candidates, small extracellular vesicles (sEVs) were isolated from the serum of liver cancer patients, liver cirrhosis patients, healthy control subjects, as well as the culture media of hepatocellular carcinoma cells (HepG2) and normal hepatocyte cells (Lo2). Isolated sEVs were confirmed by size distribution analysis, morphological analysis, and surface biomarker tests. Mass spectrometry based label-free quantification revealed 61 and 63 differentially expressed proteins in the serum sEVs of liver cirrhosis patients and liver cancer patients (p