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

• Published in: Biochimie Vol. 177; pp. 132 - 141
• Main Authors: Uzzaman, Asad, Zhang, Xuguang, Qiao, Zhi, Zhan, Hao, Sohail, Amir, Wahid, Amir, Shang, Zhi, Guan, Xin, Cao, Cheng-Xi, Xiao, Hua
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2020
• Subjects: Biomarker; biomarkers; blood serum; East Asia; Extracellular vesicles; fibrinogen; gene expression regulation; hepatocytes; hepatoma; humans; immunoassays; Liver cancer; Liver cirrhosis; mass spectrometry; morbidity; mortality; patients; Proteomics; East Asia; Biomarker; FGG; Extracellular vesicles; GO; HCC; FBLN1; THBS1; ECM; Liver cancer; LC-MS/MS; Proteomics; FASP; sEVs; NTA; Liver cirrhosis; TEM
• ISSN: 0300-9084; 1638-6183; 1638-6183
• DOI: 10.1016/j.biochi.2020.08.013

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 < 0.05), respectively. The proteomics data of cell-derived sEVs were combined for the selection of valuable candidates. Promising proteins were further verified by immunoassay, including thrombospondin-1 (THBS1), fibulin-1(FBLN1), and fibrinogen gamma chain (FGG), which could differentiate healthy control from liver cancer or liver cirrhosis. Our findings verified the hypothesis that cancer-related proteomics signatures are present in the sEVs of patient’s serum and might be monitored for the evaluation of liver cancer and liver cirrhosis. [Display omitted] •Small extracellular vesicles (sEVs) were successfully isolated from serum and cell culture medium for quantitative proteomics research.•61 and 63 significant differentially expressed proteins were discovered in serum sEVs for liver cirrhosis and liver cancer, respectively.•Serum sEVs harbor liver cancer associated proteins that could be used for non-invasive diagnostics.