Proteomic and metabolomic analyses illustrate the mechanisms of expression of the O 6 ‐methylguanine‐DNA methyltransferase gene in glioblastoma

作者：Xi Chen, Jinli Sun, Yukui Li, Weichao Jiang, Zhangyu Li, Jianyao Mao, Liwei Zhou, Sifang Chen, Guowei Tan · 发表于：CNS Neuroscience & Therapeutics · 年份：2023 · DOI：10.1111/cns.14415 · 被引用次数：5 · 研究领域：Glioma Diagnosis and Treatment、Epigenetics and DNA Methylation、Cancer, Hypoxia, and Metabolism

AIM: -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 ...