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Comparative Study
. 2018 Apr;22(4):633-639.
doi: 10.1007/s11605-017-3619-3. Epub 2017 Nov 20.

Correlation Between Postoperative Early Recurrence of Hepatocellular Carcinoma and Mesenchymal Circulating Tumor Cells in Peripheral Blood

Zhong Wang  1 , Lei Luo  1 , Yuan Cheng  1 , Guolin He  1 , Bangjian Peng  1 , Yi Gao  1 , Ze-Sheng Jiang  1 , MingXin Pan  2
Affiliations
Comparative Study

Correlation Between Postoperative Early Recurrence of Hepatocellular Carcinoma and Mesenchymal Circulating Tumor Cells in Peripheral Blood

Zhong Wang et al. J Gastrointest Surg. 2018 Apr.

Abstract

Background: Circulating 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.

Methods: CTCs 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.

Results: Of 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).

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.

Keywords: Circulating tumor cells (CTCs); Early recurrence(ER); Epithelial-mesenchymal transition (EMT); Hepatocellular carcinoma (HCC).

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Conflict of interest statement

Ethics Approval and Consent to Participate

This study was approved by the Clinical Research Ethics Committee of Zhujiang Hospital of Southern Medical University (with numbers ZJYY-2014-GDEK-002). All participants provided informed written consent prior to their entry into the study. In the case that changes in the protocol are necessary, relevant amendments are made and submitted to the ethics trial registration authorities for approval.

Competing Interests

The authors declare that they have no competing interests.

Availability of Data and Materials

Please contact the author for data requests.

Figures

Fig. 1
Fig. 1
ROC curves of different circulating tumor cell subtypes
Fig. 2
Fig. 2
HCC patients without portal vein tumor thrombus: log-rank test for time to recurrence with mesenchymal CTC-positive or negative postoperatively
See this image and copyright information in PMC

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