Long-term dynamics of extracellular vesicles as recurrence markers in hepatocellular carcinoma patients following surgical tumor resection

Background: Hepatocellular carcinoma (HCC) is a prevalent malignant liver tumor, and its incidence has been rising globally, causing a significant number of cancer-related deaths. Unfortunately, curative treatments are only possible for a small fraction of patients. Recent studies suggest that Extracellular Vesicles (EVs) released by HCC cells may play a crucial role in the tumor's spread and growth, and thus, they have the potential to provide promising solutions to current diagnostic limitations.

Aims: The objective of this study is to investigate the feasibility of utilizing EVs as new biomarkers for the early detection of HCC and for predicting its recurrence after undergoing HCC resection.

Materials and methods: A prospective cohort study was carried out at a single center, involving 37 patients diagnosed with HCC and 20 patients with non-malignant liver disease (NMLD) serving as the control group. The study aimed to analyze the peripherally circulating EVs of both groups at three different time points: 1) before surgery, 2) one day after surgery, and 3) 12 months after surgery, to determine if EVs could serve as novel biomarkers for early HCC diagnosis and recurrence after HCC resection. The study utilized microbead-based magnetic particle sorting and fluorescence-activated cell scanning (FACS) to detect 37 characteristic surface proteins of EVs. Moreover, HCC patients who experienced tumor recurrence (R-HCC) within 12 months after surgery were compared to HCC patients without recurrence (NR-HCC).

Results In this study, R-HCC patients (n=12/20) exhibited lower levels of CD31 expression in exosomes compared to NR-HCC patients (p=0.0033). In comparison between the HCC and NMLD patients, the NMLD group demonstrated significantly higher levels of CD41b expression (p=0.0286). Moreover, the NMLD group exhibited significantly higher preoperative CD19 ratios than postoperative (p=0.0065).

Conclusions The study provides potential targets for developing diagnostic and therapeutic methods for early and non-invasive detection of HCC recurrence. Further studies on EV profiling in HCC recurrence may aid in developing personalized therapies and improving treatment outcomes. A better understanding of EVs can provide valuable insights into the prevention, diagnosis, and prognosis of HCC.

Publication History

Article published online:
28 August 2023