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Radiofrequency ablation-increased CXCL10 is associated with earlier recurrence of hepatocellular carcinoma by promoting stemness

  • Original Article
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Tumor Biology

Abstract

Radiofrequency ablation (RFA) represents a valuable choice in hepatocellular carcinoma (HCC); however, local recurrence of HCC is common after RFA. Here, 20 primary HCC patients treated by RFA were enrolled. Before (termed 0d) and after RFA treatment for 1 and 7 days (termed 1d and 7d, respectively), plasma and noncancerous tissue were collected. ELISA assay showed that plasma C-X-C motif chemokine 10 (CXCL10) was increased in ten patients (type I patients) but decreased in the other 10 patients (type II patients). The mean interval for HCC recurrence in type I patients was less than the mean interval in type II patients. Interestingly, a significant negative correlation between interval for HCC recurrence and fold change of plasma CXCL10 (1d/0d or 7d/0d) was identified, suggesting that RFA-induced CXCL10 is associated with earlier HCC recurrence. Immunofluorescence assay showed that the receptor of CXCL10, chemokine (C-X-C motif) receptor 3 (CXCR3), was significantly increased in type I, but not type II, patients after RFA. In vitro assay demonstrated that CXCL10 stimulus increased the rate of CD133+ cancer stem cells (CSCs) in HepG2 cells by binding to CXCR3 and then inducing c-Myc expression. Many studies have reported that induction of CD133+ CSCs contributes to HCC recurrence. Thus, CXCL10-increased CD133+ CSCs by activating CXCR3/c-Myc pathway might accelerate HCC recurrence after RFA. These data might have potential implications for HCC therapy.

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Abbreviations

CSCs:

Cancer stem cells

CXCL10:

C-X-C motif chemokine 10

CXCR3:

Chemokine (C-X-C motif) receptor 3

HCC:

Hepatocellular carcinoma

MSCs:

Mesenchymal stem cells

RFA:

Radiofrequency ablation

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (812111545), the Twelfth Key Science and Technology Five-Year Plan of China (2012ZX10001-002, 2012ZX10001-003, and 2012ZX10001-004), the National Key Technology Support Program of China (2012BAI15B08), the Capital Health Research and Development Special (2014-1-1151), and the Project of Construction of Innovative Teams and Teacher Career Development for Universities and Colleges Under Beijing Municipality (IDHT20150502).

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    Authors and Affiliations

    1. Beijing You’an Hospital, Capital Medical University, No. 8 XiTouTiao, YouAnMenWai Street, FengTai District, Beijing, 100069, China

      Yabo Ouyang, Kai Liu, Meijun Hao, Rongling Zheng, Chunmiao Zhang, Yanning Wu, Xiaofeng Zhang, Ning Li, Jiasheng Zheng & Dexi Chen

    2. Beijing Institute of Hepatology, Beijing, 100069, China

      Yabo Ouyang, Kai Liu, Rongling Zheng, Chunmiao Zhang, Yanning Wu, Xiaofeng Zhang, Ning Li & Dexi Chen

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    1. Yabo Ouyang
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    Correspondence to Jiasheng Zheng or Dexi Chen.

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    Yabo Ouyang and Kai Liu contributed equally to this work.

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    Ouyang, Y., Liu, K., Hao, M. et al. Radiofrequency ablation-increased CXCL10 is associated with earlier recurrence of hepatocellular carcinoma by promoting stemness. Tumor Biol. 37, 3697–3704 (2016). https://doi.org/10.1007/s13277-015-4035-5

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    • DOI: https://doi.org/10.1007/s13277-015-4035-5

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