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

• Published in: Annals of surgical oncology 2012-07, Vol.19 (Suppl 3), p.375-384
• Main Authors: Chen, Rongxin, Cui, Jiefeng, Xu, Changde, Xue, Tongchun, Guo, Kun, Gao, Dongmei, Liu, Yinkun, Ye, Shenglong, Ren, Zhenggang
• Format: Article
• Language: English
• Subjects: alpha-Fetoproteins - metabolism; Biomarkers, Tumor - metabolism; Carcinoma, Hepatocellular - enzymology; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; Cell Line, Tumor; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms - enzymology; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Male; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medicine; Medicine & Public Health; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Recurrence, Local - enzymology; Oncology; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Surgery; Surgical Oncology; Tissue Array Analysis; Translational Research and Biomarkers; Up-Regulation
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-011-1836-7

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.