The proteomic response in glioblastoma in young patients

Abstract

Increasing age is an important prognostic variable in glioblastoma (GBM). We have defined the proteomic response in GBM samples from 7 young patients (mean age 36 years) compared to peritumoural-control samples from 10 young patients (mean age 32 years). 2-Dimensional-gel-electrophoresis, image analysis, and protein identification (LC/MS) were performed. 68 proteins were significantly altered in young GBM samples with 29 proteins upregulated and 39 proteins downregulated. Over 50 proteins are described as altered in GBM for the first time. In a parallel analysis in old GBM (mean age 67 years), an excellent correlation could be demonstrated between the proteomic profile in young GBM and that in old GBM patients (r2 = 0.95) with only 5 proteins altered significantly (p < 0.01). The proteomic response in young GBM patients highlighted alterations in protein–protein interactions in the immunoproteosome, NFkB signalling, and mitochondrial function and the same systems participated in the responses in old GBM patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-014-1474-6) contains supplementary material, which is available to authorized users.

Exploring the differences in metabolic behavior of astrocyte and glioblastoma: a flux balance analysis approach

“…Also, through the in silico approach, we tried to gain some insight into the alternative metabolic routes and metabolites which contributed to the metabolic heterogeneity of glioblastoma. The present model was capable of yielding results which were in correspondence to the experimentally proved phenomena of both astrocytes and glioblastoma (Deighton et al 2014;Mangia et al 2009;Marrif and Juurlink 1999;Pellerin and Magistretti 1994;Wise et al 2008;Zhou et al 2011). From our study, specific pathways were observed to demonstrate a co-operative effect in the astrocyte and glioblastoma scenarios.…”

“…For the verification of the objective function-'GBM_BM' in representing the properties of glioblastoma, a qualitative analysis was performed to compare the activity of certain reported reactions in the astrocytic and glioblastoma scenario. The fold change in activity from astrocytic to glioblastoma scenario as predicted from the model was compared to existing proteome data extracted from young glioblastoma patients (Deighton et al 2014). The results of this comparison are listed in Table 1.…”

Proteomic Advances in Glial Tumors through Mass Spectrometry Approaches

“…Other important individual prognostic factors are the age of diagnosis, the Karnofsky performance status and the methylation status of the MGMT promoter gene [65]. A comparative proteomic analysis of young and old glioblastoma patients identified multiple differentially expressed proteins involved in the regulation of the tumorigenesis that could explain the prognostic differences between young and old glioblastoma patients [38]. Among the differentially expressed proteins of special interest is the Phosphatidylethanolamine-binding protein 1 (PEBP1), an inhibitor to both Raf/MEK/ERK and nuclear factor kappa B pathways [66].…”

“…Among the differentially expressed proteins of special interest is the Phosphatidylethanolamine-binding protein 1 (PEBP1), an inhibitor to both Raf/MEK/ERK and nuclear factor kappa B pathways [66]. PEPB1 was up-regulated in young glioblastoma and down-regulated in old glioblastoma patients [38]. The regulation differences of PEPB1 between young and old glioblastoma patients should be further investigated to understand its influence on prognosis.…”

Effects of glycogen synthase kinase inhibitor on glioblastoma multiforme cell line via apoptosis and cell signaling pathways

“…It has also been shown that NF-kB induces cancer development and tumor progression by inducing a proinflammatory microenvironment and even leads to chemotherapy resistance (4,43). NF-kB regulates protein transcription for the down-regulation of apoptosis and increases cell invasion, angiogenesis, and vascular permeability in the cell nucleus (12). Chin et al reported the neuroprotector effect of GSK-3 inhibition in that it reduces neuronal death (8).…”