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Prognostic significance and mechanisms of patterned matrix vasculogenic mimicry in hepatocellular carcinoma

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Abstract

Vasculogenic mimicry (VM), including tubular VM and patterned matrix VM, has been generally recognized as a new pattern of tumor neovascularization. Pilot studies of tubular VM showed that it was present in hepatocellular carcinoma (HCC) and associated with poor clinical prognosis. However, whether patterned matrix VM is clinically significant in HCC is unknown. To elucidate the effects of patterned matrix VM on prognosis of HCC and the mechanisms involved in VM formation, we examined 151 cases of surgically resected human HCC by immunohistochemistry and transmission electron microscopy and conducted hypoxic experiments on human HCC cell line MHCC97-H. We observed 31 of 151 (20.5%) cases exhibited evidence of patterned matrix VM. The expression of patterned matrix VM was associated with larger tumors (P = 0.042), vascular invasion (P = 0.016), high-grade HCC (P = 0.022), and late-stage HCC (P = 0.013). Kaplan–Meier survival analysis revealed that cases of the VM group had lower overall survival (OS) rate (P < 0.001) and disease-free survival (DFS) rate (P = 0.002) than that of the non-VM group. Univariate and multivariate analysis indicated that the presence of patterned matrix VM was independent adverse prognostic factor for both OS (P = 0.004) and DFS (P = 0.011). Expression of hypoxia-inducible factor 1 alpha (HIF-1alpha), matrix metalloproteinase (MMP)-2, and MMP-9 were higher in the VM group than in the non-VM group (P = 0.001, P = 0.030, P = 0.007, respectively). After VM formation was induced by hypoxia, up-regulated expression of HIF-1α, MMP-2, and MMP-9 was also detected in cells cultured under hypoxia condition. Our results indicate that patterned matrix VM exists in HCC, and it might serve as an unfavorable prognostic factor for HCC patients. It is possible that hypoxia via induction of expression of HIF-1alpha, MMP-2, and MMP-9 may enhance VM formation in HCC.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (30972892), the Science and Technology Key Project of Anhui Province (07010302193), Anhui Provincial Natural Science Foundation (090413107), Anhui Provincial College Natural Science Key Project (KJ2009A178), the Science and Technological Fund of Anhui Province for Outstanding Youth (08040106818), and the Anhui Provincial ‘‘115’’ Industrial Innovation Program.

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Authors and Affiliations

  1. Graduate School of Tianjin Medical University, 300070, Tianjin, People’s Republic of China

    Wen-bin Liu

  2. Centre for the Study of Liver Cancer and Department of Hepatic Surgery, Anhui Provincial Hospital, Anhui Medical University, No. 17, Lujiang Road, 230001, Hefei, People’s Republic of China

    Wen-bin Liu, Ge-liang Xu, Wei-dong Jia, Jian-sheng Li, Jin-liang Ma, Yong-sheng Ge, Wei-hua Ren, Ji-hai Yu, Wei Wang & Xiu-jun Wang

  3. Department of Pathology, Anhui Provincial Hospital, Anhui Medical University, 230001, Hefei, People’s Republic of China

    Ke Chen & Zhi-hua Wang

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  1. Wen-bin Liu
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Correspondence to Ge-liang Xu.

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Wen-bin Liu and Wei-dong Jia contributed equally to this work.

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Liu, Wb., Xu, Gl., Jia, Wd. et al. Prognostic significance and mechanisms of patterned matrix vasculogenic mimicry in hepatocellular carcinoma. Med Oncol 28 (Suppl 1), 228–238 (2011). https://doi.org/10.1007/s12032-010-9706-x

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  • DOI: https://doi.org/10.1007/s12032-010-9706-x

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