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Influence of preoperative transcatheter arterial chemoembolization on gene expression in the HIF-1α pathway in patients with hepatocellular carcinoma

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Although transcatheter arterial chemoembolization (TACE) is the most common treatment option in patients with hepatocellular carcinoma (HCC), its clinical benefits remain still controversial. Since TACE induces hypoxic necrosis in tumors, hypoxia-inducible factor 1α (HIF-1α) could critically affect biology in residual tumors after TACE treatment and subsequent prognosis. However, HIF-1α and its prognostic relevance in TACE have rarely been examined in human specimens. In the current study, we investigated the prognosis and expression of genes regulated by HIF-1α in HCC patients receiving preoperative TACE for the first time.

Methods

In total, 35 patients with HCC (10 patients undergoing preoperative TACE) were retrospectively studied. The prognostic significance of TACE was analyzed using Kaplan–Meier and Cox regression models. Protein levels of HIF-1α and mRNA levels of HIF-1α-associated genes were examined using immunohistochemistry (IHC) and real-time RT-PCR, respectively.

Results

Preoperative TACE was significantly associated with increased 2-year recurrence rate (80 vs. 36 %, P = 0.00402) and shorter disease-free survival (DFS) time (11.9 vs. 35.7 months, P = 0.0182). TACE was an independent prognostic factor for recurrence (P = 0.007) and poor DFS (P = 0.010) in a multivariate analysis. Immunohistochemical staining revealed in vivo activation of HIF-1α in human specimens treated with TACE. Notably, protein levels of HIF-1α were significantly increased in TACE tissues demonstrated by IHC. Transcriptional targets of HIF-1α showed mRNA expression patterns consistent with activation of HIF-1α in TACE tissues.

Conclusions

Our findings collectively demonstrate that preoperative TACE confers poor prognosis in HCC patients through activation of HIF-1α.

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Acknowledgments

This work was supported by 2010 Grant from Department of Medical Sciences, The Graduate School, Ajou University and grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare (1320240), Republic of Korea.

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Authors and Affiliations

  1. Department of Surgery, Ajou University School of Medicine, Suwon, 443-721, Korea

    Weiguang Xu, Yong Keun Park, Bong Wan Kim & Hee Jung Wang

  2. CbsBioscience, Inc., 59-5 Jang-Dong, Yuseong-gu, Daejeon, 305-343, Korea

    Jung-Hee Kwon, Young Ho Moon & Yun Suk Yu

  3. Department of Pathology, Ajou University School of Medicine, Suwon, 443-721, Korea

    Young Bae Kim

  4. Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea

    Namgyu Lee & Kwan Yong Choi

  5. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gil Medical Center, Gachon University, Incheon, 405-760, Korea

    Yun Soo Kim

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  1. Weiguang Xu
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Correspondence to Hee Jung Wang.

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Weiguang Xu and Jung-Hee Kwon have contributed equally to this work.

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Xu, W., Kwon, JH., Moon, Y.H. et al. Influence of preoperative transcatheter arterial chemoembolization on gene expression in the HIF-1α pathway in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 140, 1507–1515 (2014). https://doi.org/10.1007/s00432-014-1713-4

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  • DOI: https://doi.org/10.1007/s00432-014-1713-4

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