We previously reported observing GLI3 in medulloblastomas expressing neuronal markers (NM) and/or glial fibrillary acidic protein (GFAP). Furthermore, patients with medulloblastomas expressing NM or GFAP tended to show favorable or poor prognosis, respectively. In the present study, we focused on the role of topoisomerase IIβ (TOP2β) as a possible regulator for neuronal differentiation in medulloblastomas and examined the pathological roles of GLI3, NM, GFAP, and TOP2β expressions in a larger population. We divided 124 medulloblastomas into three groups (NM−/GFAP−, NM +/GFAP−, and GFAP +) based on their immunoreactivity (IR) against NM and GFAP. The relationship among GLI3, NM, GFAP, and TOP2β was evaluated using fluorescent immunostaining and a publicly available single-cell RNA sequencing dataset. In total, 87, 30, and 7 medulloblastomas were classified as NM−/GFAP−, NM + /GFAP−, and GFAP +, and showed intermediate, good, and poor prognoses, respectively. GLI3-IR was frequently observed in NM +/GFAP− and GFAP + , and TOP2β-IR was frequently observed only in NM +/GFAP− medulloblastomas. In fluorescent immunostaining, TOP2β-IR was mostly co-localized with NeuN-IR but not with GFAP-IR. In single-cell RNA sequencing, TOP2β expression was elevated in CMAS/DCX-positive, but not in GFAP-positive, cells. NM-IR and GFAP-IR are important for estimating the prognosis of patients with medulloblastoma; hence they should be assessed in clinical practice.

我们之前报道过在表达神经元标记物 (NM) 和/或神经胶质纤维酸性蛋白 (GFAP) 的成神经管细胞瘤中观察到 GLI3。此外，表达 NM 或 GFAP 的髓母细胞瘤患者往往分别表现出良好或不良的预后。在本研究中，我们关注拓扑异构酶 IIβ（TOP2β）作为髓母细胞瘤中神经元分化的可能调节因子的作用，并检查了 GLI3、NM、GFAP 和 TOP2β 表达在更大人群中的病理作用。我们根据它们对 NM 和 GFAP 的免疫反应性 (IR) 将 124 个髓母细胞瘤分为三组（NM-/GFAP-、NM +/GFAP- 和 GFAP +）。使用荧光免疫染色和公开可用的单细胞 RNA 测序数据集评估 GLI3、NM、GFAP 和 TOP2β 之间的关系。总共 87, 30, 和 7 个髓母细胞瘤被分类为 NM-/GFAP-、NM + /GFAP- 和 GFAP +，分别显示中等、良好和不良预后。GLI3-IR 在 NM +/GFAP- 和 GFAP + 中经常观察到，TOP2β-IR 仅在 NM +/GFAP- 髓母细胞瘤中经常观察到。在荧光免疫染色中，TOP2β-IR 主要与 NeuN-IR 共定位，但不与 GFAP-IR 共定位。在单细胞 RNA 测序中，TOP2β表达在CMAS / DCX阳性细胞中升高，但在GFAP阳性细胞中没有升高。NM-IR和GFAP-IR对于估计髓母细胞瘤患者的预后很重要；因此，应在临床实践中对其进行评估。