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Chinese Journal of Oncology Prevention and Treatment ›› 2017, Vol. 9 ›› Issue (1): 55-60.doi: 10.3969/j.issn.1674-5671.2017.01.11

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Detection and classification of circulating tumor cells in hepatocellular carcinoma patients and their clinical significance

  

  1. Department of Hepatobiliary Surgery,Affiliated Tumor Hospital of Guangxi Medical University;Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center;Key Laboratory of High-Incidence-Tumor Early Prevention and Treatment,Ministry of Education
  • Online:2017-02-25 Published:2017-03-24
  • Contact: Li Lequn.E-mail:Li_lequn@263.com

Abstract:

 Objective To explore the distribution of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) patients and to analyze their relationship with HCC clinical stage and prognosis after surgery. Methods CanPatrolTM CTC-enrichment and in situ hybridization (ISH) were used to isolate,identify and classify CTCs from the blood of 112 HCC patients and 20 healthy donors. Blood was collected from HCC patients at 1 or 2 days before resection as well as 8-10 days after resection. Results CTCs were detected in 101(90.18%) HCC patients but not in any of the healthy donors. CTCs were classified into five subpopulations based on EMT markers: epithelial CTCs(E-CTC),epithelial-predominant hybrid CTCs(E>M-CTC),epithelial/mesenchymal hybrid CTCs(E≈M-CTC),mesenchymal-predominant hybrid CTCs(M>E-CTC)and mesenchymal CTCs(M-CTC).CTC count and M-CTC percentage were closely related to BCLC stage of HCC. The cut-off value of 16 for CTC count predicted early recurrence with sensitivity of 55.3%,specificity of 92.3% and AUC of 0.74. The cut-off value of 2% for M-CTC percentage predicted recurrence with sensitivity of 80.9%,specificity of 69.2% and AUC of 0.748. Tumor-free survival analyses indicated that patients with both CTC count≥16 and M-CTC≥2% showed significantly lower tumor-free survival than patients with both CTC count<16 and M-CTC<2% and patients with only CTC count≥16 or M-CTC≥2%. Postoperative levels were measured in all 112 patients at 8-10 days following resection. CTC count dropped after surgery,whereas M-CTC percentage increased. Patients in whom M-CTC percentage increased,showed significantly shorter tumor-free survival than patients in whom M-CTC percentage decreased or stayed the same(P<0.05). In 10 patients monitored postoperatively for CTC changes,8 displayed an increase in CTC count at 1-2 months before recurrence or appearance of metastatic lesions. Conclusions CTCs were detected in a high percentage of HCC patients,including early-stage HCC patients,suggesting that tumor dissemination may be an early event. Patients with high CTC count and/or M-CTC percentage and patients in whom M-CTC percentage increased after surgery show lower tumor-free survival and worse prognosis. Postoperative monitoring of changes in CTC counts after surgery may allow early prediction of recurrence.

Key words: Liver neoplasms , Circulating tumor cells, Epithelial-mesenchymal transition, Recurrence , Metastasis, Prognosis