Mestnik Shelby, Sorajja Natali, Lu Zhanni, Mills Lauren J, Williams Lindsay
Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
J Cell Mol Med. 2024 Dec;28(24):e70286. doi: 10.1111/jcmm.70286.
Ependymoma is the second most common malignant paediatric brain tumour composed of nine methylation-defined, clinically relevant subgroups. It is unclear if there are sex differences in methylation profiles within these subgroups which could guide future treatment options. We obtained available methylation data from the National Center for Biotechnology Information Gene Expression Omnibus (GEO). Differentially methylated probes (DMPs) between sexes were identified in each ependymoma sample and mapped to genes. Reactome pathways resulting from genes were identified. Survival was estimated for each sex within molecular subgroups. There were 492 cases included in the main analysis: PF-EPN-A (n = 238) PF-EPN-B (n = 52), PF-SE (n = 34), SP-MPE (n = 26), SP-EPN (n = 21), ST-EPN-RELA (n = 87), ST-EPN-YAP1 (n = 13) and ST-SE (n = 21). Females were observed to have better, but statistically nonsignificant, 5-year overall survival (OS) and better, marginally significant 5-year progression-free survival (PFS) than males. One subgroup, ST-EPN-RELA, showed significantly better OS in females. There was a difference in immune cell composition within tumour subgroups. One gene, RFTN1, was consistently differentially methylated by sex among all subgroups. There were biologic pathways identified from genes with differential methylation by sex in the following subgroups: PF-EPN-B, PF-SE, ST-EPN-RELA and ST-EPN-YAP1. Many of the identified pathways may be options for potential therapeutic targets.
室管膜瘤是第二常见的儿童恶性脑肿瘤，由九个甲基化定义的、具有临床相关性的亚组组成。目前尚不清楚这些亚组内的甲基化谱是否存在性别差异，而这可能会指导未来的治疗方案。我们从美国国立生物技术信息中心基因表达综合数据库（GEO）获取了可用的甲基化数据。在每个室管膜瘤样本中鉴定出性别间差异甲基化探针（DMPs），并将其映射到基因上。确定了由这些基因产生的Reactome通路。估计了分子亚组内各性别的生存率。主要分析纳入了492例病例：幕上室管膜瘤A型（PF-EPN-A，n = 238）、幕上室管膜瘤B型（PF-EPN-B，n = 52）、幕上室管膜下瘤（PF-SE，n = 34）、脊髓髓内室管膜瘤（SP-MPE，n = 26）、脊髓室管膜瘤（SP-EPN，n = 21）、幕下室管膜瘤RELA融合型（ST-EPN-RELA，n = 87）、幕下室管膜瘤YAP1融合型（ST-EPN-YAP1，n = 13）和幕下室管膜下瘤（ST-SE，n = 21）。观察到女性的5年总生存率（OS）较好但无统计学意义，5年无进展生存率（PFS）较好且有边缘显著性，均优于男性。其中一个亚组，幕下室管膜瘤RELA融合型，女性的OS显著更好。肿瘤亚组内免疫细胞组成存在差异。一个基因，RFTN1，在所有亚组中性别间均持续存在差异甲基化。在以下亚组中鉴定出了由性别差异甲基化基因产生的生物学通路：幕上室管膜瘤B型、幕上室管膜下瘤、幕下室管膜瘤RELA融合型和幕下室管膜瘤YAP1融合型。许多鉴定出的通路可能是潜在治疗靶点的选择。
