IDH 野生型胶质母细胞瘤 (GBM) 患者的预后很差。在这里，我们分析了肿瘤整体 DNA 甲基化的潜在预后价值。将 492 个原发样本和 31 个复发样本（均接受联合治疗）以及 148 个仅接受放射治疗的原发样本的 DNA 甲基化与患者生存率进行了比较。我们确定了平均甲基化值并根据甲基化数据估计了免疫细胞浸润。此外，还对 23 个 GBM 细胞系的平均整体 DNA 甲基化进行了分析，并与通过集落形成测定测量的细胞放射敏感性相关。高平均 DNA 甲基化水平与生存改善相关，这与已知的风险因素（MGMT 启动子甲基化、年龄）相关。 ，切除范围；p=0.009）和甲基化亚组。值得注意的是，这种相关性也与免疫细胞浸润无关，因为免疫细胞数量较多确实与显着更好的 OS 相关，但平均甲基化较低。放射敏感性 GBM 细胞系的平均甲基化水平显着高于耐药细胞系 (p=0.007)，并且仅接受放射治疗的患者 OS 的改善也与较高的 DNA 甲基化相关 (p=0.002)。此外，与匹配的原发肿瘤样本相比，复发 GBM 样本显示平均 DNA 甲基化显着降低 (p=0.041)。我们的结果表明，平均整体 DNA 甲基化与胶质母细胞瘤的结果独立相关。数据还表明，较高的 DNA 甲基化与更好的放疗反应和较低的侵袭性表型相关，这两者可能有助于观察到与 OS 的相关性。© 作者 2023。由牛津大学出版社代表协会出版用于神经肿瘤学。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

The IDH wild type glioblastoma (GBM) patients have a devastating prognosis. Here, we analyzed the potential prognostic value of global DNA methylation of the tumors.DNA methylation of 492 primary samples and 31 relapsed samples, each treated with combination therapy, and of 148 primary samples treated with radiation alone were compared with patient survival. We determined the mean methylation values and estimated the immune cell infiltration from the methylation data. Moreover, the mean global DNA methylation of 23 GBM cell lines was profiled and correlated to their cellular radiosensitivity as measured by colony formation assay.High mean DNA methylation levels correlated with improved survival, which was independent from known risk factors (MGMT promoter methylation, age, extent of resection; p=0.009) and methylation subgroups. Notably, this correlation was also independent of immune cell infiltration since higher number of immune cells indeed was associated with significantly better OS but lower mean methylation. Radiosensitive GBM cell lines had a significantly higher mean methylation than resistant lines (p=0.007), and improved OS of patients treated with radiotherapy alone was also associated with higher DNA methylation (p=0.002). Furthermore, specimens of relapsed GBM revealed a significantly lower mean DNA methylation compared to the matching primary tumor samples (p=0.041).Our results indicate that mean global DNA methylation is independently associated with outcome in glioblastoma. The data also suggest that a higher DNA methylation is associated with better radiotherapy response and less aggressive phenotype, both of which presumably contribute to the observed correlation with OS.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.