The Impact of MMP-2 and Its Specific Inhibitor TIMP-2 Expression on the WHO Grade and Prognosis of Gliomas in Chinese Population: a Meta-Analysis

Abstract

So far, the prognostic value of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) expressions in patients with gliomas has been widely reported, especially in China. But, the results were inconsistent. Thus, we conducted a meta-analysis to determine the correlation of MMP-2 and TIMP-2 expressions with the prognosis of patients with gliomas. Identical search strategies were used to search relevant literature in electronic databases updated to May 1, 2015, and odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were estimated. Funnel plots and Egger’s tests were conducted for the evaluation of publication bias, and heterogeneity and sensitivity were also analyzed. Finally, a total of 25 studies involving 1572 patients were included in the meta-analysis. Coincidentally, all these studies were conducted in Chinese population. It was found that MMP-2 expression was significantly associated with high-WHO grade gliomas (n = 24, OR = 6.54, CI = 4.98–8.60; I 2 = 0 %, P = 0.911) and poor overall survival (OS), while it did not correlate to age (n = 2, OR = 0.78, CI = 0.35–1.74; I 2 = 0 %, P = 0.621) and gender (n = 2, OR = 1.15, CI = 0.51–2.62; I 2 = 0 %, P = 0.995). Moreover, the results of the pooled analysis indicated that there was no association between TIMP-2 expression and the WHO grade of gliomas (n = 7, OR = 1.02, 95 % CI = 0.68–1.54; I 2 = 71.4 %, P = 0.002), but the ratio of MMP-2 and TIMP-2 (MMP-2/TIMP-2) rose with the increase of the WHO grade of gliomas. In conclusion, there was no correlation between TIMP-2 expression and the WHO grade of gliomas, while MMP-2 expression was potently associated with high-WHO grade of gliomas.

MMP-2 expression and correlation with pathology and MRI of glioma

“…It was manifested that MMP-2 was expressed at low level in gliomas with small diameter and low malignancy, but it was highly expressed in malignant gliomas with larger diameter. These results are similar to the findings of other scholars (14). It can be seen that MMP-2 exerts its pathological effects by means of its abnormal expression in brain glioma.…”

Pharmacological Inhibition of CA-IX Impairs Tumor Cell Proliferation, Migration and Invasiveness

“…CA-IX inhibitors caused an evident decrease of MMP-2 activity, visualized as smaller and less intense degradation bands. These data are further confirmed by the release of TIMP-2, an endogenous inhibitor of the metalloprotease activity and tumor cell invasiveness [29,42,43]. In fact, an increase of TIMP-2 is observed under the same treatment condition that causes the decrease of MMP-2 activity, in both MDA-MB-231 and A549 cells.…”

The Role of microRNAs in Multidrug Resistance of Glioblastoma

“…It is reported that the co-culture of U87MG astrocytoma cells and human neural stem cell-derived astrocytes led to the induction of malignant-like phenotypes in astrocytes acquired from tumor cells by inducing the expression of GFAP, MMP-2, TGF-B1, SPARC, and CX43 [51]. Moreover, co-culturing of MSCs with U87MG simultaneously leads to a decrease in MMP inhibitor (TIMP-2) expression, indicating that U87MG could elevate a modification of the phenotype of neighboring astrocytes which may provide a significant change to the extracellular matrix of the tumor microenvironment and allow tumor invasion [52,53]. In addition, it was suggested that a certain miRNA was shared between normal and glioblastoma cells.…”