From the Department of Pathology, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
J Neuropathol Exp Neurol. 2022 Jan 21;81(1):54-60. doi: 10.1093/jnen/nlab124.
Patients with IDH-wildtype glioblastoma (GBM) generally have a poor prognosis. However, there is an increasing need of novel robust biomarkers in the daily clinico-pathological setting to identify and support treatment in patients who become long-time survivors. Jumonji domain-containing protein 6 (JMJD6) is involved in epigenetic regulation of demethylation of histones and has been associated with GBM aggressiveness. We investigated the expression and prognostic potential of JMJD6 tumor fraction score in 184 IDH-wildtype GBMs. Whole-slides were double-stained with an antibody against JMJD6 and an exclusion-cocktail consisting of 4 antibodies (CD31, SMA, CD45, and Iba-1), enabling evaluation of tumor cells only. Stainings were quantified with a combined software- and scoring-based approach. For comparison, IDH-mutated WHO grade II, III and IV astrocytic gliomas were also stained, and the JMJD6 tumor fraction score increased with increasing WHO grade, although not significantly. In multivariate analysis including age, gender, performance status and post-surgical treatment high JMJD6 tumor fraction score was associated with longer overall survival in IDH-wildtype GBMs (p = 0.03), but the effect disappeared when MGMT promoter status was included (p = 0.34). We conclude that JMJD6 is highly expressed in IDH-wildtype GBM but it has no independent prognostic value.
IDH 野生型胶质母细胞瘤（GBM）患者的预后通常较差。然而，在日常临床病理环境中，需要新型强大的生物标志物来识别和支持那些成为长期幸存者的患者的治疗。含有 Jumonji 结构域的蛋白 6（JMJD6）参与组蛋白去甲基化的表观遗传调控，与 GBM 的侵袭性有关。我们研究了 184 例 IDH 野生型 GBM 中 JMJD6 肿瘤分数评分的表达和预后潜力。使用针对 JMJD6 的抗体和包含 4 种抗体（CD31、SMA、CD45 和 Iba-1）的排除鸡尾酒对全切片进行双重染色，仅评估肿瘤细胞。使用软件和评分相结合的方法对染色进行定量。为了比较，还对 IDH 突变的 WHO 二级、三级和四级星形细胞瘤进行了染色，JMJD6 肿瘤分数评分随着 WHO 分级的增加而增加，尽管没有显著差异。在包括年龄、性别、表现状态和手术后治疗的多变量分析中，高 JMJD6 肿瘤分数评分与 IDH 野生型 GBM 的总生存期延长相关（p=0.03），但当包括 MGMT 启动子状态时，这种相关性消失（p=0.34）。我们的结论是，JMJD6 在 IDH 野生型 GBM 中高度表达，但它没有独立的预后价值。
