Millesi Matthias, Ryba Alice Senta, Hainfellner Johannes A, Roetzer Thomas, Berghoff Anna Sophie, Preusser Matthias, Heller Gerwin, Tomasich Erwin, Sahm Felix, Roessler Karl, Wolfsberger Stefan
Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
Comprehensive Cancer Center, Central Nervous System Unit, Medical University of Vienna, Vienna, Austria.
Front Oncol. 2022 Mar 9;12:811729. doi: 10.3389/fonc.2022.811729. eCollection 2022.
Accounting for 15-20% of all meningiomas, WHO grade II meningiomas represent an intermediate group regarding risk of tumor recurrence. However, even within this subgroup varying clinical courses are observed with potential occurrence of multiple recurrences. Recently, DNA methylation profiles showed their value for distinguishing biological behaviors in meningiomas. Therefore, aim of this study was to investigate DNA methylation profiles in WHO grade II meningiomas.
All patients that underwent resection of WHO grade II meningiomas between 1993 and 2015 were screened for a dismal course clinical course with ≥2 recurrences. These were matched to control cases with benign clinical courses without tumor recurrence. DNA methylation was assessed using the Infinium Methylation EPIC BeadChip microarray. Unsupervised hierarchical clustering was performed for identification of DNA methylation profiles associated with such a dismal clinical course.
Overall, 11 patients with WHO grade II meningiomas with ≥2 recurrences (Group dismal) and matched 11 patients without tumor recurrence (Group benign) were identified. DNA methylation profiles revealed 3 clusters-one comprising only patients of group dismal, a second cluster comprising mainly patients from group benign and a third cluster comprising one group dismal and one group benign patient. Based on differential methylation pattern associations with the Wnt and the related cadherin signaling pathway was observed.
DNA methylation clustering showed remarkable differences between two matched subgroups of WHO grade II meningiomas. Thus, DNA methylation profiles may have the potential to support prognostic considerations regarding meningioma recurrence and radiotherapeutic treatment allocation after surgical resection.
世界卫生组织（WHO）二级脑膜瘤占所有脑膜瘤的15%-20%，在肿瘤复发风险方面属于中间组。然而，即使在这个亚组中，也观察到不同的临床病程，可能会出现多次复发。最近，DNA甲基化谱显示出其在区分脑膜瘤生物学行为方面的价值。因此，本研究的目的是调查WHO二级脑膜瘤的DNA甲基化谱。
对1993年至2015年间接受WHO二级脑膜瘤切除术的所有患者进行筛查，以确定临床病程不佳且复发≥2次的患者。将这些患者与临床病程良性且无肿瘤复发的对照病例进行匹配。使用Infinium甲基化EPIC BeadChip微阵列评估DNA甲基化。进行无监督层次聚类以识别与这种不良临床病程相关的DNA甲基化谱。
总体而言，确定了11例WHO二级脑膜瘤复发≥2次的患者（不良组）和匹配的11例无肿瘤复发的患者（良性组）。DNA甲基化谱显示出3个聚类——一个仅包含不良组的患者，第二个聚类主要包含良性组的患者，第三个聚类包含1例不良组患者和1例良性组患者。基于差异甲基化模式，观察到与Wnt和相关钙黏蛋白信号通路的关联。
DNA甲基化聚类在WHO二级脑膜瘤的两个匹配亚组之间显示出显著差异。因此，DNA甲基化谱可能有潜力支持关于脑膜瘤复发的预后考虑以及手术切除后的放射治疗分配。
