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Prognostic value of purinergic P2X7 receptor expression in patients with hepatocellular carcinoma after curative resection

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Tumor Biology

Abstract

The family of type 2 purinergic (P2) receptors, especially P2X7, is responsible for the direct tumor-killing functions of extracellular adenosine triphosphate (ATP), but the precise role of P2X7 in the progression of hepatocellular carcinoma (HCC) remains elusive. This study aims to evaluate prognostic value of P2X7 expression in HCC patients after surgical resection. Expression of P2X7 was assessed by immunohistochemistry in tissue microarrays containing paired tumor and peritumoral liver tissues from 273 patients with HCC who had undergone hepatectomy between 2006 and 2007. Prognostic value of P2X7 expression and clinical outcomes were evaluated. Peritumoral P2X7 expression was significantly higher than intratumoral P2X7 expression. No significant prognostic difference was observed for overall survival for intratumoral P2X7 density, whereas peritumoral P2X7 density indicates unfavorable overall survival in training set and BCLC stage 0-A subset. Besides, peritumoral P2X7 density, which correlated with tumor size, venous invasion, and BCLC stage, was identified as an independent poor prognosticator for overall survival and recurrence-free survival. The association was further validated in validation set. Peritumoral P2X7 is a potential unfavorable prognosticator for overall survival and recurrence free survival in HCC patients after surgical resection. Further external validation and functional analysis should be pursued to evaluate its potential prognostic value and therapeutic significance for HCC patients.

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Acknowledgments

We thank Ms. Haiying Zeng (Department of Pathology, Zhongshan Hospital, Shanghai Medical College of Fudan University) for technical assistance. This study was funded by grants from National Basic Research Program of China (2012CB822104), National Key Projects for Infectious Diseases of China (2012ZX10002-012), National Natural Science Foundation of China (31100629, 31270863, 81472227, 81471621), Program for New Century Excellent Talents in University (NCET-13-0146), Shanghai Rising-Star Program (13QA1400300), and Postdoctoral Science Foundation of China (2012M520828, 2013T60416).

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Authors and Affiliations

  1. Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Mailbox 103, 138 Yixueyuan Road, Shanghai, 200032, China

    Haiou Liu, Weisi Liu, Zheng Liu, Yidong Liu & Jiejie Xu

  2. Department of Immunology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, China

    Weijuan Zhang

  3. Department of Urology, Zhongshan Hospital, Shanghai Medical College of Fudan University, Shanghai, 200032, China

    Le Xu

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  1. Haiou Liu
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  2. Weisi Liu
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  3. Zheng Liu
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  4. Yidong Liu
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  6. Le Xu
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  7. Jiejie Xu
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Correspondence to Jiejie Xu.

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Fig. S1

Estimated overall survival and recurrence free survival following surgery by dichotomized intratumor P2X7 expression for patients with HCC. (a), OS for training cohort; (b), RFS for training cohort; (c), OS for validation cohort; (d), RFS for validation cohort. (GIF 41 kb)

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Liu, H., Liu, W., Liu, Z. et al. Prognostic value of purinergic P2X7 receptor expression in patients with hepatocellular carcinoma after curative resection. Tumor Biol. 36, 5039–5049 (2015). https://doi.org/10.1007/s13277-015-3155-2

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  • DOI: https://doi.org/10.1007/s13277-015-3155-2

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