Glioma Pathophysiology: Insights Emerging from Proteomics

Abstract

Proteomics is increasingly employed in both neurological and oncological research to provide insight into the molecular basis of disease but rarely has a coherent, novel pathophysiological insight emerged. Gliomas account for >50% of adult primary intracranial tumors, with malignant gliomas (anaplastic astrocytomas and glioblastoma multiforme) being the most common. In glioma, the application of proteomic technology has identified altered protein expression but without consistency of these alterations or their biological significance being established. A systematic review of multiple independent proteomic analyses of glioma has demonstrated alterations of 99 different proteins. Importantly 10 of the 99 proteins found differentially expressed in glioma [PHB, Hsp20, serum albumin, epidermal growth factor receptor (EGFR), EA-15, RhoGDI, APOA1, GFAP, HSP70, PDIA3] were identified in multiple publications. An assessment of protein-protein interactions between these proteins compiled using novel web-based technology, revealed a robust and cohesive network for glioblastoma. The protein network discovered (containing TP53 and RB1 at its core) compliments recent findings in genomic studies of malignant glioma. The novel perspective provided by network analysis indicates that the potential of this technology to explore crucial aspects of glioma pathophysiology can now be realized but only if the conceptual and technical limitations highlighted in this review are addressed.

Comprehensive characterization of glioblastoma tumor tissues for biomarker identification using mass spectrometry-based label-free quantitative proteomics

“…Many of the differentially expressed proteins identified in this study have been previously reported in GBM biomarker studies using other proteomic methods including 2-DE, 2D-DIGE, and other MS-based techniques (12,31,46). In addition, we identified several new proteins that were not reported before in the context of GBM (Supplementary Table S1).…”

LC-MS/MS Analysis of Differentially Expressed Glioblastoma Membrane Proteome Reveals Altered Calcium Signaling and Other Protein Groups of Regulatory Functions

“…Several proteomic studies have also been reported providing important insights in the pathophysiology of these tumors (1,9). In our previous study, we compared whole tissue extracts from various grades of glioma with control specimens employing a two-dimensional electrophoresis-MS approach and identified 72 differentially expressed proteins, of which 27 were present in multiple tumor specimens (10).…”

TROY Interacts with Rho Guanine Nucleotide Dissociation Inhibitor α (RhoGDIα) to Mediate Nogo-induced Inhibition of Neurite Outgrowth

“…The increased TROY expression was strongly inversely related with the life span of patients (44). Meanwhile, RhoGDI␣ was found to be down-regulated in glioma cells (41,46). Furthermore, the increased TROY expression and decreased RhoGDI␣ expression were accompanied with reduced RhoA activation and increased Rac1 activation in glioma cells (44,(47)(48)(49).…”