Gliomas are fast growing and usually manifest in an aggressive infiltrative model. MMP2 overexpression is associated with brain tumor malignancy and metastasis formation. The aim of this study was to investigate the influence of MMP2 on glioma formation and clinical outcomes by performing analysis at the DNA, RNA, and protein levels. Methylation status and mRNA level were evaluated in 162 samples; the MMP2 protein level was analyzed in 28 patient preoperative and postoperative blood samples using protein microarray analysis and conventional ELISA. The MMP2 MSP analysis revealed a gradually increasing gene promoter demethylation frequency, and the Kaplan-Meier analysis showed that the methylated gene promoter is related to longer overall survival (Log-rank test X ² = 12.508, df = 1, P < 0.0001). Relative mRNA expression was significantly downregulated when the promoter was methylated. Pairwise comparison analysis showed statistically significant (Mann-Whitney test, P < 0.05) differences in the MMP2 expression median when comparing different glioma grades. The Kaplan-Meier analysis revealed that low MMP2 expression was associated with better survival (Log-rank test X ² = 7.732, df = 1, P = 0.005). At the protein level, MMP2 expression in patient sera showed no differences between malignancy grades and patient preoperative and postoperative states, while the ELISA assay showed the tendency of accumulating MMP2 protein in higher malignancy patient sera samples. The Kaplan-Meier analysis showed the tendency of having a shorter survival time with a higher MMP2 protein level in patient sera. MMP2 has a significant role in glioma pathogenesis and could be used as a potential molecular marker for tumor progression.

Rūta Sincevičiūtė

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