Graduate Program in Principles of Surgery, Mackenzie Evangelical University, Curitiba 80730-000, PR, Brazil.
The Center for Advanced Neurology and Neurosurgery (CEANNE), Porto Alegre 90560-010, RS, Brazil.
Int J Mol Sci. 2023 Jul 18;24(14):11601. doi: 10.3390/ijms241411601.
Medulloblastoma (MB) is the most common type of malignant pediatric brain tumor. Neuropilin-1 (NRP1), encoded by the NRP1 gene, is a transmembrane glycoprotein overexpressed in several types of cancer. Previous studies indicate that NRP1 inhibition displays antitumor effects in MB models and higher NRP1 levels are associated with poorer prognosis in MB patients. Here, we used a large MB tumor dataset to examine NRP1 gene expression in different molecular subgroups and subtypes of MB. We found overall widespread NRP1 expression across MB samples. Tumors in the sonic hedgehog (SHH) subgroup showed significantly higher NRP1 transcript levels in comparison with Group 3 and Group 4 tumors, with SHH samples belonging to the α, β, Δ, and γ subtypes. When all MB subgroups were combined, lower NRP1 expression was associated with significantly shorter patient overall survival (OS). Further analysis showed that low NRP1 was related to poorer OS, specifically in MB subgroups SHH and Group 3 MB. Our findings indicate that patients with SHH and Group 3 tumors that show lower expression of NRP1 in MB have a worse prognosis, which highlights the need for subgroup-specific investigation of the NRP1 role in MB.
髓母细胞瘤（MB）是最常见的儿童脑恶性肿瘤。神经纤毛蛋白-1（NRP1）由 NRP1 基因编码，是一种在多种癌症中过度表达的跨膜糖蛋白。先前的研究表明，NRP1 抑制在 MB 模型中显示出抗肿瘤作用，并且较高的 NRP1 水平与 MB 患者的预后较差相关。在这里，我们使用了一个大型 MB 肿瘤数据集来研究不同分子亚型和亚型的 MB 中 NRP1 基因的表达。我们发现 MB 样本中普遍存在 NRP1 表达。与 Group 3 和 Group 4 肿瘤相比，声门神经鞘瘤（SHH）亚组的肿瘤 NRP1 转录本水平显著升高，SHH 样本属于 α、β、Δ 和 γ 亚型。当所有 MB 亚组合并时，NRP1 表达水平较低与患者总生存期（OS）显著缩短相关。进一步的分析表明，低 NRP1 与 OS 较差相关，特别是在 SHH 和 Group 3 MB 亚组中。我们的研究结果表明，在 MB 中显示 NRP1 表达较低的 SHH 和 Group 3 肿瘤患者预后较差，这突显了需要对 NRP1 在 MB 中的作用进行亚组特异性研究。
