Increasing evidence have demonstrated that dysregulated alternative splicing (AS) events promoted tumor development and was correlated with worse prognosis in the context of certain malignancies. Nevertheless, a comprehensive examination of the prognosis role of AS events in acute myeloid leukemia (AML) has not yet been illuminated. In this study, univariate and multivariate Cox regression analysis were used to identify survival-related AS events and independent prognostic predictors. The interaction between splicing factors (SFs) and AS events was visualized by Cytoscape. A total of 3013 survival-associated AS events in 1977 genes were screened in 151 AML patients. Interestingly, the majority (2031 events) were revealed to be protective factors. Furthermore, the prediction models were constructed for each type of AS and all of them displayed good performance in predicting prognosis, considering their area under curve values of the receiver operating characteristic were all above 0.7. Notably, the splicing regulatory network displayed the underlying interaction networks between SFs and AS events. Taken together, our study demonstrated the survival-related AS events in AML and uncovered the possible association between SFs and prognostic AS events, which provide new prognostic biomarkers and aid to develop novel targets for AML therapy.

中文翻译：

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急性髓性白血病中选择性剪接事件的预后价值的全面表征。

越来越多的证据表明，在某些恶性肿瘤的情况下，可变剪接（AS）事件失调促进了肿瘤的发展，并且与更差的预后相关。然而，尚未阐明对AS事件在急性髓性白血病（AML）中的预后作用的全面检查。在这项研究中，单因素和多因素Cox回归分析被用于识别生存相关的AS事件和独立的预后预测因子。Cytoscape可以显示剪接因子（SFs）与AS事件之间的相互作用。在151个AML患者中筛选了1977个基因中的3013个与生存相关的AS事件。有趣的是，大多数（2031事件）被发现是保护因素。此外，针对每种类型的AS构建了预测模型，并且考虑到接收器工作特性曲线值下的面积均大于0.7，因此它们在预测预后方面均表现出良好的性能。值得注意的是，拼接监管网络显示了SF和AS事件之间的潜在交互网络。综上所述，我们的研究证明了AML中与生存相关的AS事件，并揭示了SF与预后AS事件之间的可能联系，这提供了新的预后生物标志物，并有助于开发AML治疗的新靶标。