Circulating Tumor Cell Phenotype Indicates Poor Survival and Recurrence After Surgery for Hepatocellular Carcinoma

Dig Dis Sci. 2018 Sep;63(9):2373-2380. doi: 10.1007/s10620-018-5124-2. Epub 2018 Jun 21.


Background: Circulating tumors cells (CTCs) may be a promising prognostic marker for patients with malignant tumors. However, there are few reports regarding its value for hepatocellular carcinoma (HCC) patients.

Aims: To investigate CTCs with epithelial and mesenchymal phenotypes as a potential prognostic biomarker for HCC patients.

Methods: Peripheral blood samples were obtained from 165 HCC patients before radical surgery. CTCs were isolated via the CanPatrol CTC enrichment technique and classified using epithelial-mesenchymal transition (EMT) markers. The relationship of CTC phenotype with clinicopathological factors and HCC recurrence in patients was analyzed.

Results: CTC-positive status (count ≥ 2/5 mL) was found in 70.9% of the 165 HCC patients. Increased CTC number was more common in patients with higher AFP levels, multiple tumors, advanced TNM and BCLC staging, and presence of embolus or microembolus (P < 0.05). CTCs heterogeneity was noted using EMT markers. Mesenchymal CTCs were significantly correlated with high AFP levels, multiple tumors, advanced TNM and BCLC stage, presence of embolus or microembolus, and earlier recurrence (P < 0.05). The presence of mesenchymal CTCs predicted the shortest relapse-free survival, followed by mixed phenotypic CTCs, and then epithelial CTCs (P < 0.001).

Conclusion: CTC phenotype may serve as a prognostic indicator for HCC patients. CTCs assessment should include phenotypic identification tailored to characterize cells based on epithelial and mesenchymal markers.

Keywords: CTC; EMT; Liver cancer; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / surgery*
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / surgery*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / surgery*
  • Neoplastic Cells, Circulating* / pathology
  • Phenotype*
  • Prospective Studies
  • Survival Rate / trends