MicroRNA Expression in Low- and High-Grade Gliomas in Pediatric Patients and Correlation with Matrix Metalloproteinase Expression

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The glioma tumor is the most widespread malignancy of the brain worldwide. The World Health Organization (WHO) classifies gliomas into four grades (I–IV) based on the level of malignancy: low grade glioma (LGG) (WHO grades I–II) and high-grade glioma (HGG), which is further classified into anaplastic astrocytoma (AA, WHO grade III) and glioblastoma multiforme (GBM, WHO grade IV). The most common form of glioma is GBM, with a prevalence of 10000 new cases in the US. In Egypt, gliomas represent 37.3% of CNS tumors, while GBM accounts for 33.8% of all gliomas [1]. HGG is the most aggressive form of glioma due to its rapidly infiltrating growth pattern, and the mean survival is only 15.2–18 months. By contrast, LGG is associated with a good prognosis, with a 5-year survival rate of 30-70%. The poor prognosis for HGG greatly emphasizes the need to understand and identify prognostic biomarkers that can discriminate HGG from LGG to improve patient survival [2-6].

The matrix metalloproteases (MMPs) enzyme family, which plays an important role in the degradation of extracellular matrix (ECM). Accumulating evidence supports an association between MMPs and pathological conditions such as cancer cell invasion and metastasis, imparted by the ability of these enzymes to degrade the ECM of tumor cells. Previous studies have reported that MMPs participate in the invasive and aggressive behavior of glioma malignancies, and the gelatinase group, including MMP-2 and MMP-9, has drawn the most attention [7,8]. Previous studies showed that increased expression of MMP-2 and MMP-9 was significant with the degree malignancy in gliomas, which plays a role in metastasis and invasiveness of the tumor, they also showed that MMP-9 is more intense and elevated when compared to the MMP-2. Another study shows association between the MMP-9 with malignancy in glioma and formation of the angiogenesis [9,10]. Studies shows strong relation between the MMP-9 and the establishment of the angiogenic process, the switch requires proteolytic release of the vascular endothelial growth factor (VEGF) by MMP-9, followed by formation of vascular network that ease the tumor spread to various sites [11-13]. Another potential class of biomarkers that is receiving increasing attention is microRNAs (miRNAs). These are members of a large family of non-coding short single stranded RNAs ~22 nucleotides (nt) in length (range 18-25 nt) that bind to the 3' untranslated region (UTR) of protein-coding mRNAs and regulate gene expression.