Bai Zhiqun, Wang Xuemei, Zhang Zhen
Department of Ultrosonic Diagnosis, The First Affiliated Hospital of China Medical University, Shenyang, China.
Front Genet. 2022 Feb 25;13:655169. doi: 10.3389/fgene.2022.655169. eCollection 2022.
The prognosis of low-grade glioma (LGG) is different from that of other intracranial tumors. Although many markers of LGG have been established, few are used in clinical practice. M6A methylation significantly affects the biological behavior of LGG tumors. Therefore, establishment of an LGG prognostic model based on m6A methylation regulatory genes is of great interest. Data from 495 patients from The Cancer Genome Atlas (TCGA) and 172 patients from the Chinese Glioma Genome Atlas (CGGA) were analyzed. Univariate Cox analysis was used to identify methylation regulatory genes with prognostic significance. LASSO Cox regression was used to identify prognostic genes. Receiver operating characteristic (ROC) and Kaplan-Meier curves were used to verify the accuracy of the model. Gene Set Enrichment Analysis (GSEA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to identify cellular pathways that were significantly associated with the prognosis of LGG. A glioma prognostic model based on five methylation regulatory genes was established. Compared with low-risk patients, patients identified as high risk had a poorer prognosis. There was a high degree of consistency between the internal training and internal validation CGGA cohorts and the external validation TCGA cohort. Furthermore, KEGG and GSEA analyses showed that the focal adhesion and cell cycle pathways were significantly upregulated in high-risk patients. This signature could be used to distinguish among patients with different immune checkpoint gene expression levels, which may inform immune checkpoint inhibitor (ICI) immunotherapy. We comprehensively evaluated m6A methylation regulatory genes in LGG and constructed a prognostic model based on m6A methylation, which may improve prognostic prediction for patients with LGG.
低级别胶质瘤(LGG)的预后与其他颅内肿瘤不同。尽管已经建立了许多LGG的标志物,但很少用于临床实践。m6A甲基化显著影响LGG肿瘤的生物学行为。因此,基于m6A甲基化调控基因建立LGG预后模型具有重要意义。对来自癌症基因组图谱(TCGA)的495例患者和来自中国胶质瘤基因组图谱(CGGA)的172例患者的数据进行了分析。采用单因素Cox分析来识别具有预后意义的甲基化调控基因。采用LASSO Cox回归来识别预后基因。采用受试者工作特征(ROC)曲线和Kaplan-Meier曲线来验证模型的准确性。利用基因集富集分析(GSEA)和京都基因与基因组百科全书(KEGG)来识别与LGG预后显著相关的细胞通路。建立了基于五个甲基化调控基因的胶质瘤预后模型。与低风险患者相比,被确定为高风险的患者预后较差。CGGA队列的内部训练和内部验证与外部验证的TCGA队列之间具有高度一致性。此外,KEGG和GSEA分析表明,高风险患者的粘着斑和细胞周期通路显著上调。该特征可用于区分具有不同免疫检查点基因表达水平的患者,这可能为免疫检查点抑制剂(ICI)免疫治疗提供参考。我们全面评估了LGG中的m6A甲基化调控基因,并基于m6A甲基化构建了一个预后模型,这可能会改善LGG患者的预后预测。