髓母细胞瘤是最常见的儿童恶性脑肿瘤，分为四个主要分子亚组，但第3组和第4组肿瘤难以细分且预后较差。需要快速的护理点诊断和预后分析来改善髓母细胞瘤的风险分层和管理。 N6-甲基腺苷 (m6A) 是一种常见的 RNA 修饰，长链非编码 RNA (lncRNA) 在肿瘤进展中发挥核心作用，但它们对髓母细胞瘤基因表达和相关临床结果的影响尚不清楚。在这里，我们分析了 469 个髓母细胞瘤肿瘤转录组，以鉴定与 m6A 调节因子共表达的 lncRNA。使用 LASSO-Cox 分析，我们确定了与总生存率显着相关的五基因 m6A 相关 lncRNA 特征 (M6LSig)，并将其组合在预后临床列线图中。利用 67 个 m6A 相关 lncRNA 的表达，使用 XGBoost 机器学习算法生成亚组分类模型，其分类准确率≥90%，包括第 3 组和第 4 组样本。所有 M6LSig 基因与肿瘤微环境中至少一种免疫细胞类型丰度显着相关，风险评分与 CD4 初始 T 细胞丰度呈正相关，与滤泡辅助 T 细胞和嗜酸性粒细胞呈负相关。在第 3 组髓母细胞瘤细胞系 (D425-Med) 中敲除关键 m6A 写入基因 METTL3 和 METTL14 会减少细胞增殖，并上调我们在计算机分析中发现的许多 M6LSig 基因，这表明标志基因在髓母细胞瘤中具有功能。这项研究强调了 m6A 依赖性 lncRNA 在髓母细胞瘤预后和免疫反应中的关键作用，并为可在临床环境中快速部署的实用临床工具奠定了基础。© 2024。作者。

Medulloblastoma, the most common malignant pediatric brain tumor, is classified into four main molecular subgroups, but group 3 and group 4 tumors are difficult to subclassify and have a poor prognosis. Rapid point-of-care diagnostic and prognostic assays are needed to improve medulloblastoma risk stratification and management. N6-methyladenosine (m6A) is a common RNA modification and long non-coding RNAs (lncRNAs) play a central role in tumor progression, but their impact on gene expression and associated clinical outcomes in medulloblastoma are unknown. Here we analyzed 469 medulloblastoma tumor transcriptomes to identify lncRNAs co-expressed with m6A regulators. Using LASSO-Cox analysis, we identified a five-gene m6A-associated lncRNA signature (M6LSig) significantly associated with overall survival, which was combined in a prognostic clinical nomogram. Using expression of the 67 m6A-associated lncRNAs, a subgroup classification model was generated using the XGBoost machine learning algorithm, which had a classification accuracy > 90%, including for group 3 and 4 samples. All M6LSig genes were significantly correlated with at least one immune cell type abundance in the tumor microenvironment, and the risk score was positively correlated with CD4+ naïve T cell abundance and negatively correlated with follicular helper T cells and eosinophils. Knockdown of key m6A writer genes METTL3 and METTL14 in a group 3 medulloblastoma cell line (D425-Med) decreased cell proliferation and upregulated many M6LSig genes identified in our in silico analysis, suggesting that the signature genes are functional in medulloblastoma. This study highlights a crucial role for m6A-dependent lncRNAs in medulloblastoma prognosis and immune responses and provides the foundation for practical clinical tools that can be rapidly deployed in clinical settings.© 2024. The Author(s).