Triple-negative breast cancer (TNBC) is a type of breast cancer (BC) showing a high recurrence ratio and a low survival probability, which requires novel actionable molecular targets. The involvement of alternative splicing (AS) in TNBC promoted us to study the potential roles of AS events in the survival prognosis of TNBC patients.

A total of 150 TNBC patients from The Cancer Genome Atlas (TCGA) were involved in this work. To study the effects of AS in the recurrence-free survival (RFS) prognosis of TNBC, we performed the analyses as follows. First, univariate Cox regression model was applied to identify RFS-related AS events. Their host genes were analyzed by Metascape to discover the potential functions and involved pathways. Next, least absolute shrinkage and selection operator (LASSO) method was used to select the most informative RFS-related AS events to constitute an AS risk factor for RFS prognosis, which was evaluated by Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves in all the data and also in different clinical subgroups. Furthermore, we analyzed the relationships between splicing factors (SFs) and these RFS-related AS events to seek the possibility that SFs regulated AS events to influence RFS. Then, we evaluated the potential of these RFS-related AS events in the overall survival (OS) prognosis from all the above aspects.

We identified a total of 546 RFS-related AS events, which were enriched in some splicing and TNBC-associated pathways. Among them, seven RFS-related events were integrated into a risk factor, exhibiting satisfactory RFS prognosis alone and even better performance when combined with clinical tumor–node–metastasis stages. Furthermore, the correlation analysis between SFs and the seven AS events revealed the hypotheses that SRPK3 might upregulate PCYT2_44231_AA to have an effect on RFS prognosis and that three other SFs may work together to downregulate FLAD1_7874_RI to influence RFS prognosis. In addition, the seven RFS-related AS events were validated to be promising in the OS prognosis of TNBC as well.

The abnormal AS events regulated by SFs may act as a kind of biomarker for the survival prognosis of TNBC.

三阴性乳腺癌（TNBC）是一种乳腺癌（BC），具有高复发率和低生存率，需要新的可操作分子靶点。TNBC 中选择性剪接 (AS) 的参与促使我们研究 AS 事件在 TNBC 患者生存预后中的潜在作用。

来自癌症基因组图谱 (TCGA) 的总共 150 名 TNBC 患者参与了这项工作。为了研究 AS 对 TNBC 无复发生存 (RFS) 预后的影响，我们进行了如下分析。首先，应用单变量 Cox 回归模型来识别 RFS 相关的 AS 事件。Metascape 分析了它们的宿主基因，以发现潜在的功能和涉及的途径。接下来，使用最小绝对收缩和选择算子 (LASSO) 方法选择信息量最大的 RFS 相关 AS 事件构成 RFS 预后的 AS 风险因素，并通过 Kaplan-Meier (KM) 和接受者操作特征 (ROC) 进行评估) 所有数据以及不同临床亚组中的曲线。此外，我们分析了剪接因子 (SFs) 与这些 RFS 相关的 AS 事件之间的关系，以寻找 SFs 调节 AS 事件以影响 RFS 的可能性。然后，我们从上述所有方面评估了这些 RFS 相关 AS 事件在总生存期 (OS) 预后中的潜力。

我们确定了总共 546 个与 RFS 相关的 AS 事件，这些事件在一些剪接和 TNBC 相关途径中得到了丰富。其中，7 个与 RFS 相关的事件被整合为一个危险因素，单独表现出令人满意的 RFS 预后，与临床肿瘤-淋巴结-转移阶段相结合时表现更好。此外，SFs 与 7 个 AS 事件之间的相关性分析揭示了假设 SRPK3 可能上调 PCYT2_44231_AA 以影响 RFS 预后，并且其他三个 SFs 可能共同下调 FLAD1_7874_RI 以影响 RFS 预后。此外，7 个与 RFS 相关的 AS 事件也被证实在 TNBC 的 OS 预后中是有希望的。

SFs调控的异常AS事件可能作为TNBC生存预后的一种生物标志物。