Clinical value of circulating tumor cells for the diagnosis and prognosis of hepatocellular carcinoma (HCC): A systematic review and meta-analysis

Medicine (Baltimore). 2020 Oct 2;99(40):e22242. doi: 10.1097/MD.0000000000022242.


Background: To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC).

Methods: Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis.

Results: Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57-0.63), 0.95 (95%CI = 0.93-0.96), 0.36 (95%CI = 0.28-0.48), 11.64 (95%CI = 5.85-23.14), and 38.94 (95%CI = 18.33-82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55-3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89-4.86; P < .01).

Conclusion: CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Count
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / pathology*
  • Neoplasm Recurrence, Local
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Odds Ratio
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Sensitivity and Specificity
  • Survival Analysis


  • Biomarkers, Tumor