Epithelial-mesenchymal transition phenotypes of circulating tumor cells correlate with the clinical stages and cancer metastasis in hepatocellular carcinoma patients

Cancer Biomark. 2017 Dec 6;20(4):487-498. doi: 10.3233/CBM-170315.


Background: Epithelial-mesenchymal transition (EMT) plays a crucial role in circulating tumor cells (CTCs) dissemination and cancer metastasis.

Objective: To investigate the EMT phenotypes of CTCs in hepatocellular carcinoma (HCC) patients and the clinical utility in the early diagnosis of HCC metastasis and progression.

Methods: We retrospectively analyzed the count and EMT classification of CTCs detected by the CanPatrol® platform in 195 HCC patients. The clinical relevance with other pathological features was statistically evaluated.

Results: CTCs were detected in 95% of the 195 HCC patients with a range of 0-86 CTCs. Total CTCs numbers were correlated with BCLC stages, metastasis and serum AFP levels. The AUC of the ROC curve was 0.861 (95% CI: 0.782-0.940) in discriminating metastatic HCC patients with non-metastatic patients. Epithelial, hybrid and mesenchymal CTCs were found in about 53%, 83% and 57% patients, respectively. The proportion of hybrid and mesenchymal CTCs was associated with ages, BCLC stages, metastasis and AFP levels. Besides, recurrent HCC patients presented higher CTCs count and increased hybrid and mesenchymal CTCs.

Conclusions: CTCs count and EMT classification are correlated with clinical stages and metastasis of HCC, suggesting that they may be potential markers for the early diagnosis of HCC metastasis and progression.

Keywords: Circulating tumor cells; cancer metastasis; epithelial-mesenchymal transition; hepatocellular carcinoma.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Disease Progression
  • Epithelial-Mesenchymal Transition* / genetics
  • Female
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology*
  • Phenotype*
  • Recurrence
  • Tumor Burden


  • Biomarkers
  • Biomarkers, Tumor