Extracellular Vesicles Contribute to Viral-Induced Hepatocellular Carcinoma: Understanding Their Involvement in Viral Hepatitis and Their Potential as Biomarkers for Early Hepatocellular Carcinoma Detection.

Abstract

The high global prevalence of hepatitis B and hepatitis C and the poor prognosis of hepatitis B and hepatitis C-associated hepatocellular carcinoma (HCC), necessitates the early diagnosis and treatment of the disease. Recent studies show that cell-to-cell communication via extracellular vesicles (EVs) is involved in the HCC progression. The objective of the following study was to explore the role of EVs in the progression of viral-induced HCC and investigate their potential for the early diagnosis of cancer. First, the mRNA derived from EVs of HCC patients was compared to the mRNA derived from EVs from the healthy controls. Expression analysis of ANGPTL3, SH3BGRL3, and IFITM3 genes from the EVs was done. Afterward, to confirm whether hepatocytes can uptake EVs, HuH7 cells were exposed to EVs, and the expression analysis of downstream target genes (AKT, TNF-α, and MMP-9) in Huh7 cells was done. Transcriptional analysis showed that in the EVs from HCC patients, the expression levels of ANGPTL3, SH3BGRL3, and IFITM3 were significantly increased by 2.62-, 4.3-, and 9.03-folds, respectively. The downstream targets, AKT, TNF-α, and MMP-9, also showed a considerable change of 4.1-, 1.46-, and 5.05-folds, respectively, in Huh7 cells exposed to HCC EVs. In conclusion, the following study corroborates the role of EVs in HCC progression. Furthermore, the significant alteration in mRNA levels of the selected genes demonstrates their potential to be used as possible biomarkers for the early diagnosis of HCC.