Cure Brain Cancer Biomarkers and Translational Research Group, Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2031, Australia.
Adult Cancer Program, Lowy Cancer Research Centre, UNSW Sydney, Randwick, NSW 2031, Australia.
Int J Mol Sci. 2021 Nov 22;22(22):12572. doi: 10.3390/ijms222212572.
Lower-grade glioma (LGG) is a diffuse infiltrative tumor of the central nervous system, which lacks targeted therapy. We investigated the role of () methylation in LGG clinical outcomes using the TCGA-LGG transcriptomics dataset. We identified four CpG sites, cg07425555, cg26969888, cg18547299, and cg24354933, which were associated with unfavorable overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analysis after adjusting for age, gender, tumor-grade, and -mutation. In multivariate analysis, the OS and DFS hazard ratios ranged from 0.44 to 0.58 ( < 0.001) and 0.62 to 0.72 ( < 0.001), respectively, for the four CpGs. Enrichment analysis of differential gene and protein expression and analysis of 24 infiltrating immune cell types showed significantly increased infiltration in LGGs and its histological subtypes with low-methylation levels of the CpGs. High expression and low-methylation subgroups of the CpG sites were associated with significantly increased , and expressions. methylation may thus be a potential indicator of immune checkpoint blockade response, and serve as a biomarker for determining prognosis and immune subtypes in LGG.
低级别胶质瘤 (LGG) 是一种中枢神经系统弥漫浸润性肿瘤，缺乏靶向治疗。我们使用 TCGA-LGG 转录组学数据集研究了 () 甲基化在 LGG 临床结局中的作用。我们鉴定了四个与单因素和多因素分析中不利的总生存期 (OS) 和无病生存期 (DFS) 相关的 CpG 位点 cg07425555、cg26969888、cg18547299 和 cg24354933，这些 CpG 位点在调整年龄、性别、肿瘤分级和 -突变后。在多因素分析中，四个 CpG 的 OS 和 DFS 风险比范围为 0.44 至 0.58(<0.001)和 0.62 至 0.72(<0.001)。差异基因和蛋白质表达的富集分析以及 24 种浸润免疫细胞类型的分析表明，CpG 低甲基化水平的 LGG 及其组织学亚型中浸润显著增加。CpG 位点的高表达和低甲基化亚组与显著增加的 和表达相关。因此， 甲基化可能是免疫检查点阻断反应的潜在指标，并可作为确定 LGG 预后和免疫亚型的生物标志物。
