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High resolution magic angle spinning 1H NMR of childhood brain and nervous system tumours.

Wilson M, Davies NP, Brundler MA, McConville C, Grundy RG, Peet AC - Mol. Cancer (2009)

Bottom Line: Glial tumours had significantly (two tailed t-test p < 0.05) higher creatine and glutamine and lower taurine, phosphoethanolamine, phosphorylcholine and choline compared with primitive neuro-ectodermal tumours.Classification accuracy was 90%.Medulloblastomas (n = 9) had significantly (two tailed t-test p < 0.05) higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol than neuroblastomas (n = 7), classification accuracy was 94%.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Sciences, University of Birmingham, Birmingham, UK. martin@pipegrep.co.uk

ABSTRACT

Background: Brain and nervous system tumours are the most common solid cancers in children. Molecular characterisation of these tumours is important for providing novel biomarkers of disease and identifying molecular pathways which may provide putative targets for new therapies. 1H magic angle spinning NMR spectroscopy (1H HR-MAS) is a powerful tool for determining metabolite profiles from small pieces of intact tissue and could potentially provide important molecular information.

Methods: Forty tissue samples from 29 children with glial and primitive neuro-ectodermal tumours were analysed using HR-MAS (600 MHz Varian gHX nanoprobe). Tumour spectra were fitted to a library of individual metabolite spectra to provide metabolite values. These values were then used in a two tailed t-test and multi-variate analysis employing a principal component analysis and a linear discriminant analysis. Classification accuracy was estimated using a leave-one-out analysis and B632+ bootstrapping.

Results: Glial tumours had significantly (two tailed t-test p < 0.05) higher creatine and glutamine and lower taurine, phosphoethanolamine, phosphorylcholine and choline compared with primitive neuro-ectodermal tumours. Classification accuracy was 90%. Medulloblastomas (n = 9) had significantly (two tailed t-test p < 0.05) higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol than neuroblastomas (n = 7), classification accuracy was 94%. Supratentorial primitive neuro-ectodermal tumours had metabolite profiles in keeping with other primitive neuro-ectodermal tumours whilst ependymomas (n = 2) had metabolite profiles intermediate between pilocytic astrocytomas (n = 10) and primitive neuro-ectodermal tumours.

Conclusion: HR-MAS identified key differences in the metabolite profiles of childhood brain and nervous system improving the molecular characterisation of these tumours. Further investigation of the underlying molecular pathways is required to assess their potential as targets for new agents.

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PCA for all tumours. PCA scores of the fitted metabolite quantities for all tumours.
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Figure 1: PCA for all tumours. PCA scores of the fitted metabolite quantities for all tumours.

Mentions: Mean metabolite values for all PNET and glial tumours are shown in Table 1. Statistically significant differences (2 tailed t-test, p < 0.05) between PNET and glial samples were found in 6 of the 17 metabolites. Higher taurine, phosphoethanolamine, phosphorylcholine and choline together with lower creatine and glutamine were found to be the important discriminators of PNETs from glial tumours. A principal component analysis performed on all fitted metabolite quantities is shown in Figure 1. The plot shows a good splitting between PNET and glial tumours using the first two principal components. The first and second principal components accounted for 20% and 15% of the variance respectively. Linear discriminant analysis was performed on the first 3 principle component (PC) scores and provides complete separation of the two groups in the first discriminant function, Figure 2a. The corresponding metabolite coefficients are shown in Figure 2b and are dominated by the metabolites found to be significantly different on the t-tests. The classification accuracy was 90% with an error rate of 18%.


High resolution magic angle spinning 1H NMR of childhood brain and nervous system tumours.

Wilson M, Davies NP, Brundler MA, McConville C, Grundy RG, Peet AC - Mol. Cancer (2009)

PCA for all tumours. PCA scores of the fitted metabolite quantities for all tumours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651110&req=5

Figure 1: PCA for all tumours. PCA scores of the fitted metabolite quantities for all tumours.
Mentions: Mean metabolite values for all PNET and glial tumours are shown in Table 1. Statistically significant differences (2 tailed t-test, p < 0.05) between PNET and glial samples were found in 6 of the 17 metabolites. Higher taurine, phosphoethanolamine, phosphorylcholine and choline together with lower creatine and glutamine were found to be the important discriminators of PNETs from glial tumours. A principal component analysis performed on all fitted metabolite quantities is shown in Figure 1. The plot shows a good splitting between PNET and glial tumours using the first two principal components. The first and second principal components accounted for 20% and 15% of the variance respectively. Linear discriminant analysis was performed on the first 3 principle component (PC) scores and provides complete separation of the two groups in the first discriminant function, Figure 2a. The corresponding metabolite coefficients are shown in Figure 2b and are dominated by the metabolites found to be significantly different on the t-tests. The classification accuracy was 90% with an error rate of 18%.

Bottom Line: Glial tumours had significantly (two tailed t-test p < 0.05) higher creatine and glutamine and lower taurine, phosphoethanolamine, phosphorylcholine and choline compared with primitive neuro-ectodermal tumours.Classification accuracy was 90%.Medulloblastomas (n = 9) had significantly (two tailed t-test p < 0.05) higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol than neuroblastomas (n = 7), classification accuracy was 94%.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Sciences, University of Birmingham, Birmingham, UK. martin@pipegrep.co.uk

ABSTRACT

Background: Brain and nervous system tumours are the most common solid cancers in children. Molecular characterisation of these tumours is important for providing novel biomarkers of disease and identifying molecular pathways which may provide putative targets for new therapies. 1H magic angle spinning NMR spectroscopy (1H HR-MAS) is a powerful tool for determining metabolite profiles from small pieces of intact tissue and could potentially provide important molecular information.

Methods: Forty tissue samples from 29 children with glial and primitive neuro-ectodermal tumours were analysed using HR-MAS (600 MHz Varian gHX nanoprobe). Tumour spectra were fitted to a library of individual metabolite spectra to provide metabolite values. These values were then used in a two tailed t-test and multi-variate analysis employing a principal component analysis and a linear discriminant analysis. Classification accuracy was estimated using a leave-one-out analysis and B632+ bootstrapping.

Results: Glial tumours had significantly (two tailed t-test p < 0.05) higher creatine and glutamine and lower taurine, phosphoethanolamine, phosphorylcholine and choline compared with primitive neuro-ectodermal tumours. Classification accuracy was 90%. Medulloblastomas (n = 9) had significantly (two tailed t-test p < 0.05) higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol than neuroblastomas (n = 7), classification accuracy was 94%. Supratentorial primitive neuro-ectodermal tumours had metabolite profiles in keeping with other primitive neuro-ectodermal tumours whilst ependymomas (n = 2) had metabolite profiles intermediate between pilocytic astrocytomas (n = 10) and primitive neuro-ectodermal tumours.

Conclusion: HR-MAS identified key differences in the metabolite profiles of childhood brain and nervous system improving the molecular characterisation of these tumours. Further investigation of the underlying molecular pathways is required to assess their potential as targets for new agents.

Show MeSH
Related in: MedlinePlus