MicroRNA Expression Signatures and Their Correlation with Clinicopathological Features in Glioblastoma Multiforme

Abstract

The increasing interest in identifying molecular biomarkers to determine patient prognosis in glioblastoma multiforme (GBM) has resulted in several microRNA (miRNA)-based signatures able to predict progression-free and overall survival. However, the coherency between these signatures is small, and correlations to clinicopathological features other than survival are seldom seen. The aim of this study was to identify any significant relationship between miRNA signatures and clinicopathological data by combining pathological features with miRNA and mRNA analysis in fourteen GBM patients. In total, 161 miRNAs were shown to cluster the GBM tumor samples into long- and short-term-surviving patients. Many of these miRNAs were associated with differential expression in GBM, including a number of miRNAs shown to confer risk or protection with respect to clinical outcome and to modulate the mesenchymal mode of migration and invasion. An inverse relationship between miR-125b and nestin expression was identified and correlated with overall survival in GBM patients, eloquently illustrating how clinicopathological findings and molecular profiling may be a relevant combination to predict patient outcome. The intriguing finding that many of the differentially expressed miRNAs contained exosome-packaging motifs in their mature sequences suggests that we must expand our view to encompass the complex intercellular communication in order to identify molecular prognostic biomarkers and to increase our knowledge in the field of GBM pathogenesis.

The limited capacity of malignant glioma-derived exosomes to suppress peripheral immune effectors

“…These multi-vesicular endosomes are typically destined for recycling by lysosomes, but occasionally fuse with the plasma membrane and thereby release their microvesicle contents into the extracellular milieu. Exosomes contain a representative profile of the proteins, mRNAs, and microRNAs of their parent T-cells; in glioblastoma (GBM) this exosomal content reflects the tumor's unique signature of EGFR amplification, EGFRvIII mutation, IDH1 mutation R132H, TGF-β, and/or podoplanin status (Al-Nedawi et al, 2008;Graner et al, 2009;Henriksen et al, 2014;Li et al, 2013;Manterola et al, 2014;Noerholm et al, 2012;Shao et al, 2012). GBM-derived exosomes also may beckon angiogenesis during hypoxia, by delivery of proteins (e.g.…”

GLAST But Not Least—Distribution, Function, Genetics and Epigenetics of l-Glutamate Transport in Brain—Focus on GLAST/EAAT1

“…We have found hsa-miR-19b-3p that has been reported to be upregulated in serum of children with autism [67]; in fact, hsa-miR-19b-3p has been suggested as a possible candidate for circulating miRNA-based prediction-marker of autism. Among other miRNA's of interest here, hsa-miR-5585-5p was found to be associated with glioblastoma [68], hsa-miR-5095 and hsa-miR-1273a were detected in microvesicles released from glioma cells [69] and hsa-miR-136-5p was reported as associated with Alzheimer's disease [70].…”

Density-Dependent Regulation of Glioma Cell Proliferation and Invasion Mediated by miR-9

“…C, Effect of glucose deprivation on miR-9 expression in 9 L cells plated at 5000, 50,000, or 250,000 cells/cm suggests coordinated regulation of the switch. Most miRNAs simultaneously regulate multiple targets, thereby conducting multifaceted changes in protein expression [5,49,50]. Several miRNAs have been identified that correlate to clinical outcomes and modulate glioblastoma proliferation and invasion [9,[50][51][52].…”

“…Most miRNAs simultaneously regulate multiple targets, thereby conducting multifaceted changes in protein expression [5,49,50]. Several miRNAs have been identified that correlate to clinical outcomes and modulate glioblastoma proliferation and invasion [9,[50][51][52]. In an effort to elucidate the signaling mechanisms that regulate the switch from proliferation to invasion in malignant glioma, we performed LCMD to isolate glioma cells from the primary tumor and from invasive tumor islets located >100 μm from the tumor boundary.…”