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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 NB vs MB. PCA scores plot for neuroblastoma and medulloblastoma cases.
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Figure 3: PCA NB vs MB. PCA scores plot for neuroblastoma and medulloblastoma cases.

Mentions: Mean metabolite quantities for medulloblastoma and neuroblastoma are shown in Table 2. Significant differences (2 tailed t-test, p < 0.05) were found in 5 of the 17 metabolites with medulloblastomas having higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol. The PCA scores plot (Figure 3) shows a near complete separation between the medulloblastomas and neuroblatomas. LDA was performed on the first 5 principal components and the scores plot is given in Figure 4a. The first discriminant function gives a complete separation of the groups and the metabolite coefficients of this function are given in Figure 4b. Apart from the 5 metabolites which are significantly different between the tumours, high phosphoethanolamine is also found to be an important discriminant of medulloblastoma. Taurine is neither significantly different between the tumour groups nor an important discriminator between the tumour groups. The classifier accuracy was 94% with an error rate of 19%.


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 NB vs MB. PCA scores plot for neuroblastoma and medulloblastoma cases.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: PCA NB vs MB. PCA scores plot for neuroblastoma and medulloblastoma cases.
Mentions: Mean metabolite quantities for medulloblastoma and neuroblastoma are shown in Table 2. Significant differences (2 tailed t-test, p < 0.05) were found in 5 of the 17 metabolites with medulloblastomas having higher creatine, glutamine, phosphorylcholine, glycine and scyllo-inositol. The PCA scores plot (Figure 3) shows a near complete separation between the medulloblastomas and neuroblatomas. LDA was performed on the first 5 principal components and the scores plot is given in Figure 4a. The first discriminant function gives a complete separation of the groups and the metabolite coefficients of this function are given in Figure 4b. Apart from the 5 metabolites which are significantly different between the tumours, high phosphoethanolamine is also found to be an important discriminant of medulloblastoma. Taurine is neither significantly different between the tumour groups nor an important discriminator between the tumour groups. The classifier accuracy was 94% with an error rate of 19%.

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