表观遗传学的肿瘤特征正在成为胶质母细胞瘤预后标志物的焦点。这些表观遗传特征中的肿瘤内异质性是否会影响预后值尚不清楚。154名胶质母细胞瘤患者中，有120名患者作为参考集合，34名患者作为测试集合。每个肿瘤标本中测量MGMT、p15和p16启动子甲基化和miRNA表达水平（miRNA-21、miRNA-24、miRNA-26a和miRNA-181d）。作为统计基线，在三个不同参考患者的三个肿瘤标本中估计了肿瘤之间的表观遗传异质性（肿瘤间）。为了估计肿瘤内的表观遗传异质性（肿瘤内），将先前的结果与测试集合中一个胶质母细胞瘤中的三个肿瘤标本进行比较。然后将异质性水平与生存率相关联，并通过外部TCGA数据集进行验证。相比参考组，测试组MGMT启动子甲基化的异质性更少。在p15和p16甲基化方面，测试组与参考组的异质性没有差异。关于miRNA-21、miRNA-24、miRNA-26a和miRNA-181d表达的肿瘤内异质性在测试组和参考组之间没有区别。表达均一增加的miRNA-21与测试集体的总生存期缩短相关。这些发现可以通过与TCGA数据集的比较进行验证。一个胶质母细胞瘤中表观遗传特征的异质性可能与不同患者之间的异质性相同。不仅表观遗传特征的程度，而且肿瘤内的异质性程度也可能影响胶质母细胞瘤的生存。 ©2023. 作者，独家授权Springer-Verlag GmbH Austria，Springer Nature的一部分。

Epigenetic tumor features are getting into focus as prognostic markers in glioblastoma. Whether intra-tumoral heterogeneity in these epigenetic characteristics may influence prognostic value remains unclear.Of 154 patients suffering from glioblastoma, 120 patients served as reference collective, while 34 patients were compiled as test collective. MGMT, p15, and p16 promoter methylation and miRNA expression levels (miRNA-21, miRNA-24, miRNA-26a, and miRNA-181d) were measured in each tumor specimen. Serving as a statistical baseline, epigenetic heterogeneity between tumors (inter-tumoral) was estimated within a triplet of three tumor specimens from three different reference patients. For estimation of epigenetic heterogeneity within a tumor (intra-tumoral), previous results were compared to three tumor specimens within one glioblastoma of patients of the test collective. Resulting levels of heterogeneity were then correlated with survival and validated by an external TCGA data set.Heterogeneity in MGMT promoter methylation occurred less likely in the test group compared to the reference group. No difference in heterogeneity was observed between test and reference group regarding p15 and p16 methylation. Intra-tumoral heterogeneity within the test group regarding miRNA-21, miRNA-24, miRNA-26a, and miRNA-181d expression was not distinguishable from inter-tumoral heterogeneity. A homogenously increased miRNA-21 expression was associated with reduced overall survival in the test collective. The findings could be validated by comparison with TCGA datasets.Heterogeneity of epigenetic characteristics in one glioblastoma may be of the same magnitude as heterogeneity between different patients. Not only the extent of epigenetic characteristics but also the extent of intra-tumoral heterogeneity may influence survival in glioblastoma.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.