Hepatocellular carcinoma (HCC) remains a major global health burden, characterized by late diagnosis, limited therapeutic options, and high mortality rates. Conventional diagnostic tools such as serum α-fetoprotein testing and imaging lack sufficient sensitivity for early detection. In recent years, liquid biopsy has emerged as a minimally invasive approach that enables real-time molecular profiling of tumors through the analysis of circulating biomarkers such as nucleic acids, proteins, and extracellular vesicles. Recent advances have underscored exosomes—nano-sized extracellular vesicles (EVs) secreted by nearly all cell types—as pivotal mediators of intercellular communication and dynamic carriers of tumor-derived molecular information, offering exciting prospects for early cancer detection and personalized therapy. In HCC, EV microRNAs (miRNAs) participate in multiple oncogenic processes, including proliferation, angiogenesis, epithelial–mesenchymal transition, and immune modulation. Specific EV-associated miRNAs, such as miR-21, miR-122, miR-224, and miR-221, show distinctive expression profiles in HCC and correlate with tumor stage, metastasis, and patient prognosis. Moreover, panels of circulating EV-associated miRNAs demonstrate superior diagnostic accuracy compared with traditional biomarkers, underscoring their potential as non-invasive tools for early detection and disease monitoring. Their inherent stability in biofluids and resistance to enzymatic degradation further support their application in liquid biopsy approaches. Despite promising results, continued research is essential to validate EV-associated miRNA signatures and to integrate these “silent messengers” into routine clinical practice for precision management of hepatocellular carcinoma.
Caragut et al. (Wed,) studied this question.