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Prognostic Value of Matrix Metalloproteinase-1/ Proteinase-Activated Receptor-1 Signaling Axis in Hepatocellular Carcinoma

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Pathology & Oncology Research

Abstract

Matrix metalloproteinase-1 (MMP-1) is proposed to be involved in both tumor cell invasion and metastasis. MMP-1 proteolytically activates protease activated receptor-1 (PAR-1), which also plays an important role in tumor development and progression. However, it is currently unknown whether MMP-1 activation of PAR-1 has relevance to the progression of hepatocellular carcinoma (HCC). To address this problem, we investigate the clinicopathological and prognostic value of MMP-1/PAR-1 signaling axis in HCC. Immunohistochemistry assay was used to determine the expression of MMP-1 and PAR-1 proteins in normal and HCC tissues. The correlations of MMP-1 and PAR-1 expression with clinicopathological parameters were assessed by Chi-squared test. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. Cox regression was adopted for multivariate analysis of prognostic factors. MMP-1 and PAR-1 immunoreactivities were negative or low in normal liver tissues, but high in HCC tissues. PAR-1 expression was significantly correlated with that of MMP-1 (r = 0.896, p < 0.0001). The overexpression of MMP-1 and PAR-1 was significantly associated with recurrence, TNM staging and portal vein invasion of HCC. Patients with high MMP-1 and PAR-1 expression had significantly poorer overall survival (OS) (both P < 0.001) and disease-free survival (DFS) (both P < 0.001) when compared with patients with the low expression of MMP-1 and PAR-1. On multivariate analysis, MMP-1 and PAR-1 expression patterns were found to be independent prognostic factors for OS (both P < 0.001) and DFS (both P < 0.001). Our results suggest for the first time that the MMP-1/PAR-1 signaling axis might be applied as a novel marker for the prediction of recurrence and metastasis potency and a significant indicator of poor prognosis for patients with HCC.

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Acknowledgements

This work was supported by the freedom explore Program (2011QNZT206) of Central South University and by a Lotus Scholars Program (200734) of Ministry of Hunan Province, P.R.China.

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Authors and Affiliations

  1. National Hepatobiliary & Enteric Surgery Research Center, Central South University, Changsha, Hunan, 410008, Peoples Republic of China

    Mingmei Liao, Jinfeng Zhao, Yangde Zhang, Zhehai Li, Jiwei Wang & Yifeng Pan

  2. State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China

    Ping Tong

  3. Xiangya Hospital, Central South University, Changsha, Hunan, 410008, Peoples Republic of China

    Xueping Feng & Man Hu

Authors
  1. Mingmei Liao
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  2. Ping Tong
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  3. Jinfeng Zhao
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  4. Yangde Zhang
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  5. Zhehai Li
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  6. Jiwei Wang
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  7. Xueping Feng
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  8. Man Hu
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  9. Yifeng Pan
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Correspondence to Yifeng Pan.

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Mingmei Liao and Ping Tong contributed equally to this work.

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Liao, M., Tong, P., Zhao, J. et al. Prognostic Value of Matrix Metalloproteinase-1/ Proteinase-Activated Receptor-1 Signaling Axis in Hepatocellular Carcinoma. Pathol. Oncol. Res. 18, 397–403 (2012). https://doi.org/10.1007/s12253-011-9458-8

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