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The proteomic response in glioblastoma in young patients.

Deighton RF, Le Bihan T, Martin SF, Barrios-Llerena ME, Gerth AM, Kerr LE, McCulloch J, Whittle IR - J. Neurooncol. (2014)

Bottom Line: 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 (r(2) = 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neurosciences, Western General Hospital, Edinburgh, EH4 2XU, UK, Ruth.Deighton@ed.ac.uk.

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 (r(2) = 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.

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a Overview of proteomic analysis of young GBM. Over 400 spots were identified by 2D gel electrophoresis. The normalised volume represents the relative amount of protein in the spot. Each point in the graph represents the relative amount of protein in the 400 spots analysed. Table 1 lists the proteins which are significantly altered in young GBM. In contrast this graph emphasises that the levels of the majority (more than 75 %) of proteins are unaltered in young GBM. Because of the dynamic range (300 fold difference from the most abundant to the least abundant protein), data are presented as logs. There is a good correlation between young GBM and young peritumoural control (r2 = 0.85), with 22 % of the spots significantly altered (see Supplementary Table 1). b Overview of proteomic response in young GBM compared to old GBM. Over 400 spots were identified by 2D gel electrophoresis. The normalised volume represents the relative amount of protein in the spot. Each point in the graph represents the relative amount of protein in the 400 spots analysed. There is an excellent correlation between young GBM and old GBM (r2 = 0.95) with only 1 % of the spots significantly altered (5 out of 405; see text for details)
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Fig1: a Overview of proteomic analysis of young GBM. Over 400 spots were identified by 2D gel electrophoresis. The normalised volume represents the relative amount of protein in the spot. Each point in the graph represents the relative amount of protein in the 400 spots analysed. Table 1 lists the proteins which are significantly altered in young GBM. In contrast this graph emphasises that the levels of the majority (more than 75 %) of proteins are unaltered in young GBM. Because of the dynamic range (300 fold difference from the most abundant to the least abundant protein), data are presented as logs. There is a good correlation between young GBM and young peritumoural control (r2 = 0.85), with 22 % of the spots significantly altered (see Supplementary Table 1). b Overview of proteomic response in young GBM compared to old GBM. Over 400 spots were identified by 2D gel electrophoresis. The normalised volume represents the relative amount of protein in the spot. Each point in the graph represents the relative amount of protein in the 400 spots analysed. There is an excellent correlation between young GBM and old GBM (r2 = 0.95) with only 1 % of the spots significantly altered (5 out of 405; see text for details)

Mentions: A total of 405 protein spots were matched across every 2Dgel (young GBM and young peritumoural-control gels) and analysed. Logarithmic association of the 405 protein expression levels (mean normalised volumes) highlights multiple protein alterations in young GBM (Fig. 1a, Supplementary Fig. 2). 90 protein spots were altered in young GBM (versus young peritumoural-control; p ≤ 0.01) and the identity of these 90 statistically significant altered spots was established by LCMS.Fig. 1


The proteomic response in glioblastoma in young patients.

Deighton RF, Le Bihan T, Martin SF, Barrios-Llerena ME, Gerth AM, Kerr LE, McCulloch J, Whittle IR - J. Neurooncol. (2014)

a Overview of proteomic analysis of young GBM. Over 400 spots were identified by 2D gel electrophoresis. The normalised volume represents the relative amount of protein in the spot. Each point in the graph represents the relative amount of protein in the 400 spots analysed. Table 1 lists the proteins which are significantly altered in young GBM. In contrast this graph emphasises that the levels of the majority (more than 75 %) of proteins are unaltered in young GBM. Because of the dynamic range (300 fold difference from the most abundant to the least abundant protein), data are presented as logs. There is a good correlation between young GBM and young peritumoural control (r2 = 0.85), with 22 % of the spots significantly altered (see Supplementary Table 1). b Overview of proteomic response in young GBM compared to old GBM. Over 400 spots were identified by 2D gel electrophoresis. The normalised volume represents the relative amount of protein in the spot. Each point in the graph represents the relative amount of protein in the 400 spots analysed. There is an excellent correlation between young GBM and old GBM (r2 = 0.95) with only 1 % of the spots significantly altered (5 out of 405; see text for details)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig1: a Overview of proteomic analysis of young GBM. Over 400 spots were identified by 2D gel electrophoresis. The normalised volume represents the relative amount of protein in the spot. Each point in the graph represents the relative amount of protein in the 400 spots analysed. Table 1 lists the proteins which are significantly altered in young GBM. In contrast this graph emphasises that the levels of the majority (more than 75 %) of proteins are unaltered in young GBM. Because of the dynamic range (300 fold difference from the most abundant to the least abundant protein), data are presented as logs. There is a good correlation between young GBM and young peritumoural control (r2 = 0.85), with 22 % of the spots significantly altered (see Supplementary Table 1). b Overview of proteomic response in young GBM compared to old GBM. Over 400 spots were identified by 2D gel electrophoresis. The normalised volume represents the relative amount of protein in the spot. Each point in the graph represents the relative amount of protein in the 400 spots analysed. There is an excellent correlation between young GBM and old GBM (r2 = 0.95) with only 1 % of the spots significantly altered (5 out of 405; see text for details)
Mentions: A total of 405 protein spots were matched across every 2Dgel (young GBM and young peritumoural-control gels) and analysed. Logarithmic association of the 405 protein expression levels (mean normalised volumes) highlights multiple protein alterations in young GBM (Fig. 1a, Supplementary Fig. 2). 90 protein spots were altered in young GBM (versus young peritumoural-control; p ≤ 0.01) and the identity of these 90 statistically significant altered spots was established by LCMS.Fig. 1

Bottom Line: 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 (r(2) = 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neurosciences, Western General Hospital, Edinburgh, EH4 2XU, UK, Ruth.Deighton@ed.ac.uk.

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 (r(2) = 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.

Show MeSH
Related in: MedlinePlus