Extracellular vesicles as a new hope for diagnosis and therapeutic intervention for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer with a high mortality rate. Early diagnosis and treatment before tumor progression into an advanced stage is ideal. The current diagnosis of HCC is mainly based on imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging. These methods have some limitations including diagnosis in the case of very small tumors with atypical imaging patterns. Extracellular vesicles (EVs) are nanosized vesicles which have been shown to act as an important vector for cell-to-cell communication. In the past decade, EVs have been investigated with regard to their roles in HCC formation. Since these EVs contain biomolecular cargo such as nucleic acid, lipids, and proteins, it has been proposed that they could be a potential source of tumor biomarkers and a vector for therapeutic cargo. In this review, reports on the roles of HCC-derived EVs in tumorigenesis, and clinical investigations using circulating EVs as a biomarker for HCC and their potential diagnostic roles have been comprehensively summarized and discussed. In addition, findings from in vitro and in vivo reports investigating the potential roles of EVs as therapeutic interventions are also presented. These findings regarding the potential benefits of EVs will encourage further investigations and may allow us to devise novel strategies using EVs in the early diagnosis as well as for treatment of HCC in the future.

Keywords: Biomarker; Diagnosis; Exosome; Extracellular vesicle; HCC; miRNA.

FIGURE 1

The roles of HCC‐derived EVs, HCC‐derived EVs as a biomarker, and the evidence of therapeutic EVs from currently available reports. HCC cells secrete EVs that can lead to increased tumor cell proliferation, migration, chemoresistance, and decreased tumor cell apoptosis. They can also affect tumor microenvironments such as increased angiogenesis. Some of these HCC‐derived EVs can be detected in circulation, making them available for use as a diagnostic biomarker. Moreover, it is possible for EVs to be used as a therapeutic cargo to transfer therapeutic molecules into tumor cells. Several in vitro and in vivo reports have demonstrated antitumoral effects using this method. miR: microRNA; Circ: circular RNA; siRNA: signal interference RNA; ANGPT2: angiopoietin2; linc: long interceding/intergenic noncoding RNA; TUC: tumor ultraconserved RNA.