Table_3_Identification of the Role and Clinical Prognostic Value of Target Genes of m6A RNA Methylation Regulators in Glioma.XLS

m6A RNA methylation regulators can regulate the growth, progression, and invasion of glioma cells by regulating their target genes, which provides a reliable support for the m6A regulator–target axes as the novel therapeutic targets and clinical prognostic signature in glioma. This study aimed to explore the role and prognostic value of m6A RNA methylation regulators and their targets. Expression profiles and clinicopathological data were obtained from the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteome Tumor Analysis Consortium (CPTAC) datasets. Differential expression and correlation analyses were performed between normal and glioma tissues at mRNA and protein levels. Univariate Cox regression, survival, and Lasso Cox regression analyses were conducted to identify and establish the prognostic gene signature. Kaplan–Meier curve, multivariate Cox regression analysis, and ROC were utilized to evaluate the prognostic capacity of the prognostic gene signature. The correlation analysis, systematic bioinformatics analysis, and cell experiment were performed to further understand the potential underlying molecular mechanisms and drug sensitivity. Our results suggested that IGF2BP2, KIAA1429, METTL16, and METTL3, as well as 208 targets are involved in the occurrence of glioma, GBM, and LGG. YTHDF1 and 78 targets involved the occurrence of glioma and GBM, not LGG, among which 181 genes were associated with overall survival. From other findings and our cell experiment results, we demonstrated that METTL3 can activate Notch pathway and facilitate glioma occurrence through regulating its direct targets NOTCH3, DLL3, and HES1, and Notch pathway genes may serve as the potential treatment targets for glioma. Our study established and validated a seven-gene signature comprising METTL3, COL18A1, NASP, PHLPP2, TIMP1, U2AF2, and VEGFA, with a good capability for predicting glioma survival, which may guide therapeutic customization and clinical decision-making. These genes were identified to influence 81 anticancer drug responses, which further contributes to the early phase clinical trials of drug development.

m6A核糖核酸甲基化调控因子可通过调节其靶基因来调控胶质瘤细胞的生长、进展和侵袭，为m6A调控因子-靶基因轴作为胶质瘤新型治疗靶点和临床预后标志物提供了可靠依据。本研究旨在探讨m6A核糖核酸甲基化调控因子及其靶基因的作用和预后价值。通过收集中国胶质瘤基因组图谱（CGGA）、癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和临床蛋白质组肿瘤分析联盟（CPTAC）数据集，获得了表达谱和临床病理数据。在mRNA和蛋白质水平上对正常组织和胶质瘤组织进行了差异表达和相关性分析。通过单因素Cox回归、生存分析和Lasso Cox回归分析，识别并建立了预后基因标志物。利用Kaplan-Meier曲线、多因素Cox回归分析和ROC曲线来评估预后基因标志物的预后能力。通过相关性分析、系统生物信息学分析和细胞实验，进一步理解潜在的分子机制和药物敏感性。我们的结果表明，IGF2BP2、KIAA1429、METTL16、METTL3以及208个靶基因与胶质瘤、GBM和LGG的发生有关。YTHDF1和78个靶基因与胶质瘤和GBM的发生有关，而不与LGG有关，其中181个基因与总生存期相关。通过其他发现和我们的细胞实验结果，我们证明了METTL3可以通过调节其直接靶标NOTCH3、DLL3和HES1激活Notch通路，并通过调节Notch通路基因来促进胶质瘤的发生，Notch通路基因可能成为胶质瘤潜在的治疗靶点。本研究建立并验证了一个包含METTL3、COL18A1、NASP、PHLPP2、TIMP1、U2AF2和VEGFA的七个基因标志物，具有良好的预测胶质瘤预后的能力，可能指导治疗个体化和临床决策。这些基因被发现可以影响81种抗癌药物的响应，进一步为药物开发的早期临床试验做出了贡献。