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Diagnostic Value of Different Phenotype Circulating Tumor Cells in Hepatocellular Carcinoma

Journal of Gastrointestinal Surgery volume 23, pages 2354–2361 (2019)Cite this article

Abstract

Background

A growing body of research indicates that the monitoring of circulating tumor cells (CTCs) may have great significance to the diagnosis of malignant tumors, assessment of condition, selection of treatment methods, and evaluation of prognosis and has a broad range of potential applications. However, the value of CTCs with different phenotypes in the diagnosis of hepatocellular carcinoma (HCC) and assessment of patient condition remains unclear.

Methods

We collected 5 ml of peripheral blood from 176 patients who were found to have space-occupying lesions in the liver via B-ultrasound diagnosis at Zhujiang Hospital affiliated with Southern Medical University between August 2015 and October 2017 and used CanPatrol™ CTCs assay technology to isolate and count CTCs with different phenotypes in the patients’ peripheral blood. This allowed analysis of the value of CTCs with different phenotypes in the diagnosis of HCC and assessment of BCLC stage.

Results

We used CanPatrol™ CTCs assay technology to isolate different types of CTCs: epithelial CTCs (only stained for epithelial markers), mesenchymal CTCs (only stained for mesenchymal markers), mixed CTCs (stained for epithelial markers and mesenchymal markers), and total CTCs (all of the foregoing CTC phenotypes). Of 176 observed patients, 6 patients were finally diagnosed as other malignant tumor liver metastasis, 113 were diagnosed as having hepatocellular carcinoma, and 57 were diagnosed as having nonmalignant liver diseases. Furthermore, we intend to evaluate the diagnostic value of different phenotype CTCs count in discrimination between hepatocellular carcinoma and nonmalignant liver diseases. We found that CTCs of all types were significantly more numerous in the peripheral blood of the HCC group patients than in the NLD group patients (P < 0.05). Furthermore, of the different types of CTCs, total CTCs had the greatest diagnostic value (AUC 0.774; 95% CI, 0.704–0.834). A further discovery was that the AUC values for total CTCs, AFP, and a combined model (combined use of total CTCs and AFP) were 0.774 (95%CI, 0.704–0.834), 0.669 (95%CI, 0.587–0.750), and 0.821 (95%CI, 0.756–0.886). Late-stage HCC patients (BCLC stage B-C) had a higher peripheral blood mesenchymal CTC count than early-stage patients (BCLC stage 0-A) (median:1 vs 0), and mesenchymal CTCs ≥ 1 was the cut-off value for the diagnosis of BCLC stage in HCC patients (sensitivity: 66.67%, specificity: 59.46%, Youden index: 0.26).

Conclusions

Total CTCs are more effective than AFP in the diagnosis of HCC; combined use of total CTCs and AFP can enhance the sensitivity of HCC diagnosis.

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Acknowledgments

We thank Surexam Biotech (Guangzhou, China) for the technical support. We are grateful to all the patients at Zhujiang Hospital who participated in this study.

Availability of Data and Materials

Please contact author for data requests.

Funding

This work was supported by grants from Natural Science Foundation of Guangdong Province, China, No.2016A030313626. The funding had no role in the collection, analysis, and interpretation of data, design of the study, or writing of the manuscript.

Author information

Affiliations

  1. Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China

    Yuan Cheng, Yujun Tang, Guolin He, Yishi Lu & MingXin Pan

  2. Department of Interventional Vascular Surgery, the Central Hospital of Zhuzhou City, Zhuzhou, 412000, Hunan, China

    Lei Luo, Juqiang Zhang & Mantian Zhou

  3. 458th Hospital of PAL, Guangzhou, 510062, China

    Zhong Wang

Authors
  1. Yuan Cheng
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  2. Lei Luo
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  3. Juqiang Zhang
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  4. Mantian Zhou
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  5. Yujun Tang
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  6. Guolin He
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  7. Yishi Lu
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  8. Zhong Wang
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  9. MingXin Pan
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Contributions

Yuan Cheng, Lei Luo, and Juqiang Zhang contributed equally to this work and should be considered as co-first authors. Yuan Cheng, Lei Luo, Juqiang Zhang, and Mantian Zhou performed the experiments. Yujun Tang, Guolin He, and Yishi Lu collected patients’ information. Zhong Wang and MingXin Pan designed the study, edited the manuscript, and confirmed the data presented in the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to MingXin Pan.

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Competing Interests

The authors declare that they have no competing interests.

Ethics Approval and Consent to Participate

This study protocol was approved by the Institutional Review Board of the Second Affiliated Hospital of Southern Medical University (ZJYY-2015-GDEK-001). All participants will provide informed written consent prior to their entry into the study. In the case that changes in the protocol are necessary, relevant amendments will be made and submitted to the ethics trial registration authorities for approval.

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Cheng, Y., Luo, L., Zhang, J. et al. Diagnostic Value of Different Phenotype Circulating Tumor Cells in Hepatocellular Carcinoma. J Gastrointest Surg 23, 2354–2361 (2019). https://doi.org/10.1007/s11605-018-04067-y

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  • DOI: https://doi.org/10.1007/s11605-018-04067-y

Keywords

  • Hepatocellular carcinoma (HCC)
  • Nonmalignant liver diseases (NLD)
  • Circulating tumor cells (CTCs)
  • Diagnostic value