Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme

Heiland, Dieter Henrik; Mader, Irina; Schlosser, Pascal; Pfeifer, Dietmar; Carro, Maria Stella; Lange, Thomas; Schwarzwald, Ralf; Vasilikos, Ioannis; Urbach, Horst; Weyerbrock, Astrid

doi:10.1038/srep29052

Cited by 21 publications

(18 citation statements)

References 40 publications

(47 reference statements)

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“…Furthermore, cluster 1 showed a strong enrichment of oligodendrocytic differentiation. The key-metabolite was creatine, which is in line with the literature [ 33 ], where creatine was found to be highly associated with increased expression of proneural genes in a MRS in-vivo study [ 33 ]. Additionally, proneural samples were typically characterized by an up-regulation of oligodendrocytic genes as OLIG1/2 [ 19 ].…”

Section: Discussionsupporting

confidence: 85%

The integrative metabolomic-transcriptomic landscape of glioblastome multiforme

et al. 2017

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The purpose of this study was to map the landscape of metabolic-transcriptional alterations in glioblastoma multiforme. Omic-datasets were acquired by metabolic profiling (1D-NMR spectroscopy n=33 Patient) and transcriptomic profiling (n=48 Patients). Both datasets were analyzed by integrative network modeling. The computed model concluded in four different metabolic-transcriptomic signatures containing: oligodendrocytic differentiation, cell-cycle functions, immune response and hypoxia. These clusters were found being distinguished by individual metabolism and distinct transcriptional programs. The study highlighted the association between metabolism and hallmarks of oncogenic signaling such as cell-cycle alterations, immune escape mechanism and other cancer pathway alterations. In conclusion, this study showed the strong influence of metabolic alterations in the wide scope of oncogenic transcriptional alterations.

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Section: Discussionsupporting

confidence: 85%

The integrative metabolomic-transcriptomic landscape of glioblastome multiforme

et al. 2017

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“…At 7 T, however, the increased separation of the H4 spins of Gln and Glu is sufficient to resolve both signals . The larger fitting error at 7 T may incidentally reflect a smaller concentration of Gln and Glu in IDH‐mutated tumours, and thus a higher degree of fitting uncertainty . Finally, both semi‐LASER sequences in this work were designed for 2‐HG detection; therefore, further studies are required to evaluate Glu and Gln detection at this TE.…”

Section: Discussionmentioning

confidence: 99%

“…The tendency for 2‐HG/tCr to underestimate 2‐HG at 3 T relative to 7 T (or, equally, for 7 T to overestimate, see Figure B) may be a result of the shorter T 2 of Cr, whereby loss of tCr signal over 110 ms generates artefactual 2‐HG/tCr estimates, which are larger at 7 T because of the decreased T 2 values. Furthermore, the tCr content in IDH‐mutated glioma may be low in certain IDH mutant tumours . Thus, the use of tCr as a reference peak for 2‐HG may result in inaccurate measurement of concentration (see Figure B, P07).…”

Section: Discussionmentioning

confidence: 99%

A comparison of 2‐hydroxyglutarate detection at 3 and 7 T with long‐TE semi‐LASER

et al. 2018

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Abnormally high levels of the 'oncometabolite' 2-hydroxyglutarate (2-HG) occur in many grade II and III gliomas, and correlate with mutations in the genes of isocitrate dehydrogenase (IDH) isoforms. In vivo measurement of 2-HG in patients, using magnetic resonance spectroscopy (MRS), has largely been carried out at 3 T, yet signal overlap continues to pose a challenge for 2-HG detection. To combat this, several groups have proposed MRS methods at ultra-high field (≥7 T) where theoretical increases in signal-to-noise ratio and spectral resolution could improve 2-HG detection. Long echo time (long-TE) semi-localization by adiabatic selective refocusing (semi-LASER) (TE = 110 ms) is a promising method for improved 2-HG detection in vivo at either 3 or 7 T owing to the use of broad-band adiabatic localization. Using previously published semi-LASER methods at 3 and 7 T, this study directly compares the detectability of 2-HG in phantoms and in vivo across nine patients. Cramér-Rao lower bounds (CRLBs) of 2-HG fitting were found to be significantly lower at 7 T (6 ± 2%) relative to 3 T (15 ± 7%) (p = 0.0019), yet were larger at 7 T in an IDH wild-type patient. Although no increase in SNR was detected at 7 T (77 ± 26) relative to 3 T (77 ± 30), the detection of 2-HG was greatly enhanced through an improved spectral profile and increased resolution at 7 T. 7 T had a large effect on pairwise fitting correlations between γ-aminobutyric acid (GABA) and 2-HG (p = 0.004), and resulted in smaller coefficients. The increased sensitivity for 2-HG detection using long-TE acquisition at 7 T may allow for more rapid estimation of 2-HG (within a few spectral averages) together with other associated metabolic markers in glioma.

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“…This analysis integrates expression modules and metabolites, which present equal correlation values (kME and metabolite intensity values). A detailed description of WCNA is given in (24).…”

Section: Cluster Analysismentioning

confidence: 99%

Metabolic Alterations in Meningioma Reflect Clinical Course

Masalha

Daka

Woerner

et al. 2020

Preprint

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BackgroundMeningiomas are common brain tumors, defined by an innocent clinical course. However, some meningiomas reveal a malignant transformation and recur within a short time period regardless of their WHO grade. The current study aims to identify potential markers, which can discriminate between benign and malignant meningioma courses. MethodsFor this purpose, we profiled the metabolites of 43 patients with low- and high-grade meningiomas. Tumor specimens were analyzed by NMR analysis; 270 metabolites were identified and clustered with the AutoPipe algorithm. ResultsWe observed two distinct clusters marked by alterations in the glycine-serine, choline or tryptophan metabolism. Both clusters showed significant differences between WHO graduation and proliferation index.ConclusionOur findings suggest that alterations of glycine-serine are associated with a lower proliferation and frequencies of recurrent tumors. Alterations of the choline-tryptophan metabolism causes increased proliferation and recurrence is more common. Our results suggest, that tumor malignancy is reflected by metabolic alterations, which can support histological classifications in order to predict the clinical outcome of patients with meningiomas.

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Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme

Cited by 21 publications

References 40 publications

The integrative metabolomic-transcriptomic landscape of glioblastome multiforme

The integrative metabolomic-transcriptomic landscape of glioblastome multiforme

A comparison of 2‐hydroxyglutarate detection at 3 and 7 T with long‐TE semi‐LASER

Metabolic Alterations in Meningioma Reflect Clinical Course

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