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Hepatoma-derived growth factor: a novel prognostic biomarker in intrahepatic cholangiocarcinoma

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Tumor Biology

Abstract

Hepatoma-derived growth factor (HDGF) is an acidic heparin-binding protein involved in tumor progression and poor prognosis of kinds of cancers. Aimed at investigating the functions of HDGF in intrahepatic cholangiocarcinoma (IHCC), we detected the expression of HDGF by immunohistochemistry in 83 patients. Associations of HDGF with clinicopathologic features, microvascular density (MVD), and overall survival rates were further analyzed by Chi-square method, univariate or multivariate analysis. HDGF functions in IHCC proliferation, invasion, and angiogenesis were detected by MTT, transwell, and tube formation assays, respectively. As a result, we found that HDGF-positive expression rate in IHCC was 51.8 % (43/83) in IHCC. HDGF expression was significantly correlated to MVD (P = 0.031), lymphatic invasion (P = 0.030), distant metastasis (P = 0.002), and TNM stage (P = 0.037). HDGF was further identified as an independent prognostic factor in IHCC with Kaplan-Meier method (P = 0.003) and Cox-regression model (P = 0.008). Moreover, both intracellular and extracellular HDGF were proved to promote the proliferation, invasion, and angiogenesis of IHCC cell lines. In conclusion, HDGF was identified as an independent prognostic biomarker in IHCC. HDGF can promote IHCC cells progression, including proliferation, invasion, and angiogenesis, indicating HDGF could become a new promising and potential drug target of IHCC.

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Acknowledgment

This study is funded by the Outstanding Young Scientist Award Fund supported by Shandong Province (no. BS2012YY021).

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Authors and Affiliations

  1. Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, China

    Sen Guo, Hong-da Liu & Yan-feng Liu

  2. Department of General Surgery, People Hospital of Hanting, Weifang City, China

    Lei Liu

  3. Department of Surgery, Binhai Branch of Weifang Hospital of Traditional Chinese Medicine, Weifang City, China

    Qiang Sun

  4. Department of General Surgery, Wendeng Central Hospital, Weihai City, China

    Xi-jun Cui

  5. Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, 44 Wenhuaxilu, Jinan, Shandong Province, China, 250012

    Sen Guo

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  1. Sen Guo
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  2. Hong-da Liu
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  3. Yan-feng Liu
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  4. Lei Liu
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Correspondence to Sen Guo.

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Guo, S., Liu, Hd., Liu, Yf. et al. Hepatoma-derived growth factor: a novel prognostic biomarker in intrahepatic cholangiocarcinoma. Tumor Biol. 36, 353–364 (2015). https://doi.org/10.1007/s13277-014-2651-0

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  • DOI: https://doi.org/10.1007/s13277-014-2651-0

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