Abstract

BackgroundCirculating tumor cells (CTCs) have been actively studied for their functions in hepatocellular carcinoma (HCC) recurrence. However, the relationship between circulating tumor cells subtypes and hepatocellular carcinoma recurrence is still unclear. MethodsCTCs were collected from the peripheral blood of 62 postoperative HCC patients. The CTCs were isolated with a filtration-based method. Multiplex fluorescence in situ hybridization was used to characterize the CTCs based on mRNA expression levels of epithelial and mesenchymal markers. ResultsOf the 62 HCC patients, 26 were diagnosed with early recurrence (ER) and 36 did not experience recurrence. Comparison between the recurrence group and the non-recurrence group showed the total number of CTCs, mesenchymal CTCs, and mixed CTCs in the recurrence group was significantly higher than in the non-recurrence group. Receiver operator characteristic (ROC) curve analysis was performed to define the positive cutoff values as follows: total number of CTCs ≥ 4, mesenchymal CTCs ≥ 1, and mixed CTCs ≥ 3. Analysis showed that portal vein tumor thrombus (hazard ratio [HR] = 2.905, P = 0.023) and mesenchymal CTC positivity (HR = 3.453, P = 0.007) were independent risk factors for ER. The correlation between the presence of mesenchymal CTCs and time to recurrence was further examined, and the results showed significantly shortened postoperative disease-free survival in patients positive for mesenchymal CTCs (P < 0.001). ConclusionsHCC patients with positive peripheral mesenchymal CTCs have a more serious risk of ER, which could be a potential biomarker in HCC prognosis monitoring.

Highlights

  • Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and has high morbidity and mortality

  • Recurrence was defined as intrahepatic recurrence and extrahepatic metastasis from a comprehensive diagnosis based on imaging results from computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA), or positron emission tomography (PET)-CT and serum AFP level and other examinations, with or without pathological diagnosis

  • Among the patients who were negative for portal vein tumor thrombus, the probability of recurrence was significantly higher in mesenchymal Circulating tumor cells (CTCs)-positive patients than in mesenchymal CTC-negative patients (P < 0.001, Fig. 2) over increasing follow-up durations

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Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and has high morbidity and mortality. Peripheral CTC subtypes were examined in patients with HCC, and their relationship with HCC recurrence was analyzed. Circulating tumor cells (CTCs) have been actively studied for their functions in hepatocellular carcinoma (HCC) recurrence. The relationship between circulating tumor cells subtypes and hepatocellular carcinoma recurrence is still unclear. Methods CTCs were collected from the peripheral blood of 62 postoperative HCC patients. The correlation between the presence of mesenchymal CTCs and time to recurrence was further examined, and the results showed significantly shortened postoperative disease-free survival in patients positive for mesenchymal CTCs (P < 0.001). Conclusions HCC patients with positive peripheral mesenchymal CTCs have a more serious risk of ER, which could be a potential biomarker in HCC prognosis monitoring

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