Alternative splicing (AS) is a ubiquitous mechanism in which pre-mRNA can be spliced into divergent variants and involved in carcinogenesis and progression in several cancers. In the present study, we systematically profiled prognostic AS signatures involving both low grade glioma (LGG) and glioblastoma (GBM) and investigated the association of AS signatures with tumor grade and IDH1 status in glioma. Percent spliced in (PSI) values and corresponding clinical data were obtained from TCGA SpliceSeq and TCGA data portal, respectively. Prognostic AS signatures were identified using univariate and stepwise multivariate Cox regression. Heatmap analysis was performed based on prognostic AS signatures. A prognostic signature was established with 69 and 88 AS events, including specific splicing events of MUTYH, STEAP3, and CTNNB1, in LGG and GBM cohorts, respectively. The area under the curve (AUC) of the prediction model was 0.968 at 2000 days of overall survival (OS) in the LGG cohort and 0.966 at 450 days of OS in the GBM cohort. In addition, these prognostic AS signatures could complement current molecular classification, such as IDH1 mutation, 1p/19q codeletion, and ATRX loss, of glioma and further identify potential subgroups of glioma with the same molecular features. In conclusion, our study systematically profiled prognostic AS events involving both low grade glioma and glioblastoma for the first time, which also shed light on the crosstalk between AS signatures and molecular features of glioma.

选择性剪接 (AS) 是一种普遍存在的机制，其中前体 mRNA 可以剪接成不同的变体，并参与多种癌症的癌变和进展。在本研究中，我们系统地分析了涉及低级别胶质瘤 (LGG) 和胶质母细胞瘤 (GBM) 的预后 AS 特征，并研究了 AS 特征与胶质瘤中肿瘤分级和 IDH1 状态的关联。拼接百分比 (PSI) 值和相应的临床数据分别来自 TCGA SpliceSeq 和 TCGA 数据门户。使用单变量和逐步多变量 Cox 回归确定预后 AS 特征。基于预后 AS 特征进行热图分析。使用 69 和 88 个 AS 事件建立了预后特征，包括 LGG 和 GBM 队列中 MUTYH、STEAP3 和 CTNNB1 的特定剪接事件，分别。预测模型的曲线下面积 (AUC) 在 LGG 队列中总生存期 (OS) 2000 天时为 0.968，GBM 队列中 OS 450 天时为 0.966。此外，这些预后性 AS 特征可以补充目前的分子分类，如神经胶质瘤的 IDH1 突变、1p/19q 编码缺失和 ATRX 丢失，并进一步确定具有相同分子特征的潜在神经胶质瘤亚组。总之，我们的研究首次系统地描述了涉及低级别胶质瘤和胶质母细胞瘤的预后 AS 事件，这也揭示了 AS 特征与胶质瘤分子特征之间的串扰。这些预后 AS 特征可以补充当前的分子分类，例如神经胶质瘤的 IDH1 突变、1p/19q 编码缺失和 ATRX 丢失，并进一步确定具有相同分子特征的神经胶质瘤的潜在亚组。总之，我们的研究首次系统地描述了涉及低级别胶质瘤和胶质母细胞瘤的预后 AS 事件，这也揭示了 AS 特征与胶质瘤分子特征之间的串扰。这些预后 AS 特征可以补充当前的分子分类，例如神经胶质瘤的 IDH1 突变、1p/19q 编码缺失和 ATRX 丢失，并进一步确定具有相同分子特征的神经胶质瘤的潜在亚组。总之，我们的研究首次系统地描述了涉及低级别胶质瘤和胶质母细胞瘤的预后 AS 事件，这也揭示了 AS 特征与胶质瘤分子特征之间的串扰。