Proteomic and metabolomic analyses illustrate the mechanisms of expression of the O6‐methylguanine‐DNA methyltransferase gene in glioblastoma
Aim Glioblastoma (GBM) has been reported to be the most common high‐grade primary malignant brain tumor in clinical practice and has a poor prognosis. O6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation has been related to prolonged overall survival (OS) in GBM patients after temozolo...
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Published in | CNS neuroscience & therapeutics Vol. 30; no. 2; pp. e14415 - n/a |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
John Wiley & Sons, Inc
01.02.2024
John Wiley and Sons Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Aim
Glioblastoma (GBM) has been reported to be the most common high‐grade primary malignant brain tumor in clinical practice and has a poor prognosis. O6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation has been related to prolonged overall survival (OS) in GBM patients after temozolomide treatment.
Methods
Proteomics and metabolomics were combined to explore the dysregulated metabolites and possible protein expression alterations in white matter (control group), MGMT promoter unmethylated GBM (GBM group) or MGMT promoter methylation positive GBM (MGMT group).
Results
In total, 2745 upregulated and 969 downregulated proteins were identified in the GBM group compared to the control group, and 131 upregulated and 299 downregulated proteins were identified in the MGMT group compared to the GBM group. Furthermore, 131 upregulated and 299 downregulated metabolites were identified in the GBM group compared to the control group, and 187 upregulated and 147 downregulated metabolites were identified in the MGMT group compared to the GBM group. The results showed that 94 upregulated and 19 downregulated proteins and 20 upregulated and 16 downregulated metabolites in the MGMT group were associated with DNA repair. KEGG pathway enrichment analysis illustrated that the dysregulated proteins and metabolites were involved in multiple metabolic pathways, including the synthesis and degradation of ketone bodies, amino sugar and nucleotide sugar metabolism. Moreover, integrated metabolomics and proteomics analysis was performed, and six key proteins were identified in the MGMT group and GBM group. Three key pathways were recognized as potential biomarkers for recognizing MGMT promoter unmethylated GBM and MGMT promoter methylation positive GBM from GBM patient samples, with areas under the curve of 0.7895, 0.7326 and 0.7026, respectively.
Conclusion
This study provides novel mechanisms to understand methylation in GBM and identifies some biomarkers for the prognosis of two different GBM types, MGMT promoter unmethylated or methylated GBM, by using metabolomics and proteomics analyses.
This study provides novel mechanisms to understand methylation in GBM and identifies some biomarkers for the prognosis of two different GBM types, MGMT promoter unmethylated or methylated GBM, by using metabolomics and proteomics analyses. |
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Bibliography: | The first three authors contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1755-5930 1755-5949 |
DOI: | 10.1111/cns.14415 |