Metabolic Variations between Low-Grade and High-Grade Gliomas—Profiling by ¹H NMR Spectroscopy

Abstract

Altered cellular metabolism is one of the crucial hallmarks of glioma that deserves exploration, as the metabolites act as direct indicators of protein function and genetic variations. The current study focused on the metabolomic profiling of patients from whom glioma specimens were obtained for the identification of specific metabolites that could distinguish the low grade and high grade. In the current study, 1H NMR spectroscopy was carried out and the data were analyzed by partial least-squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). Pathway analysis was done to associate characteristic metabolites with the grades of sample using MetaboAnalyst 4.0 software based on the KEGG metabolic pathways database. Distinctive metabolic profiles among low- and high-grade gliomas with top 15 characteristic metabolites that could discriminate these grades were identified on the basis of their VIP scores from the OPLS-DA model. The major altered metabolic pathways include choline, taurine and hypotaurine, glutamate/glutamine, glutathione, and phenyl alanine/tyrosine, which were found to be consistent with the particular grade of a sample. Our study clearly demonstrated a characteristic metabolic profile of individual grades of glioma, suggesting that an altered metabolism is consistent with the specific grades of glioma appreciation and could lead to the development novel treatment strategies.

Metabolic Alterations Related to Glioma Grading Based on Metabolomics and Lipidomics Analyses

“…Meanwhile, the remaining 12 important metabolites were significantly decreased, and they were mainly lipids including LPEs, PSs and PI ( Figures 2C and 3A). Amino acids and other metabolic alterations associated with glioma grading have been reported in previous studies [13,15,20], but few studies have focused on lipids. Interestingly, gene clustering analysis found that the profile of lipid metabolism-related genes showed obvious differences between low-grade and high-grade gliomas, and low-grade gliomas exhibited an enrichment in the phosphatidylinositol metabolism process [17].…”

“…Investigation of metabolic alterations among different grades of glioma tissues could provide insight into molecular mechanisms associated with glioma progression, and may suggest potential chances for glioma prevention, diagnosis, and treatment [11,12]. Some researchers have reported that the key metabolic alterations related to glioma grading include glutamate metabolism, choline metabolism and cysteine metabolism [13][14][15][16]. Although there are increasing reports on the metabolites related to glioma grading, the results for metabolic alterations are still equivocal.…”

The Effect of Prickly Ash (Zanthoxylum bungeanum Maxim) on the Taste Perception of Stewed Sheep Tail Fat by LC-QTOF-MS/MS and a Chemometrics Analysis

“…The PLS-DA model was used to select the metabolites and separate the groups (soup groups, fat block groups and upper oil layer groups) with the parameter of VIP > 1, FC > 2 and p < 0.05. A cross-validation (R 2 and Q 2 ) was used to verify the stability of the model and a permutation test (1000 cycles) was used to prove that the model was not overfitting [19].…”

Dysregulated Alanine as a Potential Predictive Marker of Glioma—An Insight from Untargeted HRMAS-NMR and Machine Learning Data

“…Previously, a targeted analysis of plasma metabolites using mass spectrometric methods identified 18 statistically significant metabolites that could differentiate LGG from the HGG samples [ 23 , 24 , 25 ]. Another study reported three plasma metabolites that were found to be associated with survival in GBM patients [ 26 , 27 ].…”