The proteomic response in glioblastoma in young patients.

Ruth F Deighton,Lorraine E Kerr,Sarah F Martin,Ian R Whittle,James Mcculloch,Thierry Le Bihan,Martin E Barrios-Llerena,Alice M J Gerth

doi:10.1007/s11060-014-1474-6

Ruth F Deighton, Lorraine E Kerr + Show 6 more

Open Access

https://doi.org/10.1007/s11060-014-1474-6

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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.

Highlights

Patients diagnosed with Glioblastoma (GBM, WHO-IV) have extremely poor median survival times, despite modern microsurgery, chemoradiotherapy, reoperation and experimental therapies [1,2,3,4]
We have defined the proteomic response in GBM samples from 7 young patients compared to peritumoural-control samples from 10 young patients. 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
The present study provides a powerful example of how proteomics can reliably test a hypothesis and demonstrates that proteomics can play an important role in understanding GBM pathophysiology

Summary

Introduction

Patients diagnosed with Glioblastoma (GBM, WHO-IV) have extremely poor median survival times, despite modern microsurgery, chemoradiotherapy, reoperation and experimental therapies [1,2,3,4]. To improve GBM treatment and patient median survival times, fresh insight into the molecular pathogenesis of GBM is essential. Multiple discrepancies between mRNA and proteomic expression profiles in differential analyses of gliomas highlight the importance of studying protein expression [7]. Long term survivors of GBM are invariably younger patients [8,9,10], and in one randomised clinical trial, median survival for GBM cohorts aged \45 years was 48 weeks compared to 19 weeks for those [65 years; and at 18 months 23 % of the younger cohort was alive compared to 3 % of the older cohort [8]. Numerous randomised controlled trials and hospital series have excluded differences in access to health care as the cause for this differential outcome [1, 9,10,11,12]

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