P08.43 Understanding the aggressive nature of glioblastoma tumors associated with the subventricular zone

Abstract

INTRODUCTION: Subventricular zone (SVZ) in the brain is niche of neural stem cells. From recent reports it is evident that the glioma patients with tumors (both low-grade and high-grade glial tumors) in close proximity to the SVZ region (SVZ+) exhibit lower survival rate than those patients with tumors away from the SVZ region (SVZ-). In order to understand the molecular features responsible for aggressive nature of SVZ+ tumors over SVZ-tumors, serum and tissue proteomic analyses of glioblastomas (GBM) were performed. MATERIALS AND METHODS: Serum proteomic analysis of SVZ-and SVZ+ GBMs was performed using two dimensional difference gel electrophoresis (2D-DIGE) and isobaric tags for relative and absolute quantitation (iTRAQ) methods. Tissue proteomic analysis of SVZ-and SVZ+ GBMs was performed using 2D-DIGE method, whereas in iTRAQ method, SVZ-and SVZ+ GBM tissue proteins were compared with peri-tumoral control tissue proteins. Validation of a few significantly altered proteins was performed using immunoblotting approach. RESULTS: Serum levels of lipid binding proteins like apolipoproteins and acute phase proteins like hemopexin and alpha-1-antichymotrypsin were found to be altered in SVZ+ GBMs with respect to SVZ-GBMs. Tissue proteomic analysis revealed various metabolic pathways affected in SVZ-and SVZ+ GBMs, which includes glycolysis, gluconeogenesis, complement and coagulation cascades, aminoacid metabolism, extracellular matrix-receptor interactions etc. Various DNA repair enzymes like X-ray repair cross-complementing proteins and histone proteins were found to be highly up-regulated in SVZ-GBMs with respect to SVZ+ GBMs, while proteins like thymosin beta-4-like protein 3, alpha-1-antitrypsin, ferritin heavy and light chains and haptoglobin which are associated with the aggressive nature of tumors were found to be up-regulated in SVZ+ GBMs with respect to SVZ-GBMs. CONCLUSIONS: Increased tumor levels of various proteins associated with cell proliferation, migration, invasion and anti-apoptosis, while decreased levels of apoptotic and DNA damage repairing enzymes in SVZ+ GBMs provides a plausible explanation to their increased aggressiveness over SVZ-GBM tumors. Further understanding of these complex subtypes of GBM tumors can prove beneficial towards development of therapeutic targets and in deciding treatment modalities.