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The Significance of MMP-9 Over MMP-2 in HCC Invasiveness and Recurrence of Hepatocellular Carcinoma After Curative Resection

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The extracellular matrix metalloproteases MMP-9 and MMP-2 are critical for the invasive potential of tumors. However, it is not clear which of the two plays the predominant role in tumor invasion and progression. In the present study, we compared the clinical efficacy of MMP-9 and MMP-2 overexpression for predicting tumor recurrence and survival after surgical resection in HCC patients.

Materials and Methods

MMP-9 and MMP-2 expression in HCC cell lines and in vitro HCC invasion model were detected by quantitative RT-PCR and immunofluorescence. The expression levels of MMP-9 and MMP-2 were assessed by immunohistochemistry in HCC tissue microarrays from HCC patients (study set) who underwent curative resection. The clinicopathological data were retrospectively analyzed. The results were further verified in an independent cohort of 92 HCC patients (validation set).

Results

Univariate analysis demonstrated that high expression of MMP-9 was associated with both time to recurrence (TTR, P = .015) and overall survival (OS, P = .024), whereas high expression of MMP-2 was only correlated with TTR (P = .041). Multivariate analysis confirmed that MMP-9 expression was an independent predictor of TTR and OS. The coindex of MMP-9 and preoperative serum AFP levels was significantly correlated with TTR and OS (P = .036 and P = .040), but the coindex of MMP-2 and AFP did not show prognostic significance for either TTR or OS (P = .067 and P = .053). The prognostic value of MMP-9 overexpression was validated in the independent data set.

Conclusion

MMP-9 is superior to MMP-2 for the prediction of tumor recurrence and survival in HCC patients after surgical resection.

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Acknowledgment

The authors sincerely thank Professors Jia Fan, Jian Zhou, Shuang-Jian Qiu, and Zhi-Quan Wu for their help in collecting human HCC tissue samples. This study was sponsored by grants from National Natural Science Foundation of China (No. 30772062, No. 81071902, and No. 81000909), China National High-Tech Research and Development Program (2006AA02A-308), China National Key Projects for Infectious Disease (2008ZX10002-021 and 2008ZX 10002-017), Shanghai Pujiang Program (No.08PJ140300), and Shanghai Natural Science Foundation (09ZR1406400).

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Authors and Affiliations

  1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

    Rongxin Chen MD, PhD, Jiefeng Cui MD, PhD, Tongchun Xue MD, PhD, Kun Guo MD, PhD, Dongmei Gao BMSC, Yinkun Liu MD, PhD, Shenglong Ye MD, PhD & Zhenggang Ren MD, PhD

  2. Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, People’s Republic of China

    Rongxin Chen MD, PhD, Jiefeng Cui MD, PhD, Tongchun Xue MD, PhD, Kun Guo MD, PhD, Dongmei Gao BMSC, Yinkun Liu MD, PhD, Shenglong Ye MD, PhD & Zhenggang Ren MD, PhD

  3. Department of Nuclear Medicine, Shanghai Fengxian District Center Hospital, Shanghai, People’s Republic of China

    Changde Xu MD, PhD

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  1. Rongxin Chen MD, PhD
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  2. Jiefeng Cui MD, PhD
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Correspondence to Zhenggang Ren MD, PhD.

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Rongxin Chen and Jiefeng Cui contributed equally to this work.

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Chen, R., Cui, J., Xu, C. et al. The Significance of MMP-9 Over MMP-2 in HCC Invasiveness and Recurrence of Hepatocellular Carcinoma After Curative Resection. Ann Surg Oncol 19 (Suppl 3), 375–384 (2012). https://doi.org/10.1245/s10434-011-1836-7

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