Medulloblastoma, a common malignant brain tumor in children, comprises four molecular subgroups WNT, SHH, Group 3, and Group 4. In the present study, we performed a deep proteome-based investigation of SHH, Group 3 and Group 4 tumors. The adult SHH medulloblastomas were found to have a distinct proteomic profile. Several RNA metabolism-related pathways including mRNA splicing, 5′ to 3′ RNA decay, 3′ to 5′ RNA decay by the RNA exosome, and the N6-methyladenosine modification of RNA were enriched in adult SHH tumors. The heightened expression of the RNA surveillance pathways is likely to be essential for the viability of adult SHH subgroup medulloblastomas, which carry mutations in U1snRNA encoding gene and thus could be a vulnerability of these tumors. Group 3 and Group 4 medulloblastomas, on the other hand, are known to have an overlap in their expression profiles and underlying genetic alterations. Group 3 proteome was found to be distinctively enriched in several metabolic pathways including glycolysis, gluconeogenesis, glutamine anabolism, glutathione-mediated anti-oxidant pathway, and drug metabolism pathway suggests that the extensive metabolic rewiring is likely to be responsible for the aggressive clinical behavior of Group 3 tumors. This comprehensive proteomic analysis has provided valuable insight into the biology of Group 3 and adult SHH medulloblastomas, which could be further explored for effective treatment of these tumors.

髓母细胞瘤是儿童常见的恶性脑肿瘤，包括四个分子亚组 WNT、SHH、第 3 组和第 4 组。在本研究中，我们对 SHH、第 3 组和第 4 组肿瘤进行了基于蛋白质组的深入研究。发现成人 SHH 髓母细胞瘤具有独特的蛋白质组学特征。几种与 RNA 代谢相关的途径，包括 mRNA 剪接、5' 到 3' RNA 衰变、RNA 外泌体的 3' 到 5' RNA 衰变以及 RNA 的 N6-甲基腺苷修饰在成人 SHH 肿瘤中富集。RNA 监测通路的高表达可能对成人 SHH 亚组成神经管细胞瘤的生存能力至关重要，其携带 U1snRNA 编码基因突变，因此可能是这些肿瘤的脆弱性。另一方面，第 3 组和第 4 组髓母细胞瘤，已知它们的表达谱和潜在的遗传改变有重叠。发现第 3 组蛋白质组在多种代谢途径中明显富集，包括糖酵解、糖异生、谷氨酰胺合成代谢、谷胱甘肽介导的抗氧化途径和药物代谢途径，这表明广泛的代谢重组可能是第3组肿瘤。这种全面的蛋白质组学分析为第 3 组和成人 SHH 髓母细胞瘤的生物学提供了宝贵的见解，可以进一步探索这些肿瘤的有效治疗。谷胱甘肽介导的抗氧化途径和药物代谢途径表明广泛的代谢重新布线可能是第 3 组肿瘤侵袭性临床行为的原因。这种全面的蛋白质组学分析为第 3 组和成人 SHH 髓母细胞瘤的生物学提供了宝贵的见解，可以进一步探索这些肿瘤的有效治疗。谷胱甘肽介导的抗氧化途径和药物代谢途径表明广泛的代谢重新布线可能是第 3 组肿瘤侵袭性临床行为的原因。这种全面的蛋白质组学分析为第 3 组和成人 SHH 髓母细胞瘤的生物学提供了宝贵的见解，可以进一步探索这些肿瘤的有效治疗。