Extracellular vesicles as potential biomarkers for diagnosis and recurrence detection of hepatocellular carcinoma: A pilot study

Abstract

Abstract Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. However, current diagnostic tools are often invasive and technically limited. Extracellular vesicles (EVs), which play vital roles in HCC growth and metastasis, serving as potential novel biomarkers. Molecular analysis of peripherally EVs could be revolutionary for early tumor diagnosis and detecting tumor recurrence. A prospective single-center cohort study including 37 HCC patients and 20 patients with non-malignant liver disease (NMLD), as a control group, was conducted. Peripherally EVs of both groups were analyzed before and after liver surgery. The study utilized microbead-based magnetic particle sorting and flow cytometry to detect 37 characteristic surface proteins of EVs. Furthermore, HCC patients who experienced tumor recurrence (R-HCC) within 12 months after surgery were compared to HCC patients without recurrence (NR-HCC). R-HCC patients (n = 12/20) showed significantly lower levels of CD31 compared to NR-HCC patients (p = 0.0033). The NMLD-group showed significantly higher expressions of CD41b than the HCC group (p = 0.0286). The study determined significant short-term changes in CD19 dynamics in the NMLD-group, with preoperative values being significantly higher than postoperative values (p = 0.0065). This finding of our pilot study suggests EVs as potential targets for the development of diagnostic and therapeutic approaches for the early and non-invasive detection of HCC recurrence by monitoring the dynamics of specific EVs markers, such as CD41b and CD31, in HCC patients. Overall, the potential of EVs as diagnostic and therapeutic targets for HCC recurrence represents a promising area of research that could have a significant impact on the management of this disease in the future.