Colon cancer is a common malignant tumor with a poor prognosis. Abnormal alternative splicing (AS) events played a part in the occurrence and metastasis of the tumor. We aimed to develop a survival-associated AS signature in colon cancer. The Percent Spliced In values of AS events were available in The Cancer Genome Atlas (TCGA) SpliceSeq database. Univariate Cox analysis was carried out to detect the prognosis-related AS events. We created a predictive model on account of the survival-associated AS events, which was further validated with a training-testing group design. Kaplan-Meier analysis was applied to assess patient survival. The area under curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive values of this model. Meanwhile, the clinical relevance of the signature and its regulatory relationship with splicing factors (SFs) were also evaluated. In total, 2132 survival-related AS events were identified from colon cancer samples. We developed an eleven-AS signature, in which the 5-year AUC value was 0.911. Meanwhile, the AUC values at five years were 0.782 and 0.855 in the testing and entire cohort, respectively. Multivariate Cox regression displayed that the T category and the risk score of the signature were independent risk factors of colon cancer survival. Also, we constructed an SFs-AS network based on 11 SFs and 48 AS events. We identified an eleven-AS signature of colon cancer. This signature could be treated as an independent prognostic factor.

中文翻译：

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确定替代剪接签名是结肠癌的独立因素。

结肠癌是常见的恶性肿瘤，预后较差。异常的可变剪接（AS）事件在肿瘤的发生和转移中起作用。我们的目标是在结肠癌中开发与生存相关的AS签名。在癌症基因组图谱（TCGA）SpliceSeq数据库中可以找到AS事件的“剪接入百分比”值。进行单因素Cox分析以检测与预后相关的AS事件。我们根据与生存相关的AS事件创建了一个预测模型，并通过训练测试小组设计对其进行了进一步验证。Kaplan-Meier分析用于评估患者生存率。执行接收器工作特性（ROC）的曲线下面积（AUC）以评估该模型的预测值。与此同时，还评估了签名的临床相关性及其与剪接因子（SF）的调节关系。从结肠癌样本中总共鉴定出2132例与生存相关的AS事件。我们开发了11个AS签名，其中5年AUC值为0.911。同时，在测试和整个队列中，五年的AUC值分别为0.782和0.855。多元Cox回归显示，T类别和签名的风险评分是结肠癌生存的独立危险因素。此外，我们基于11个SF和48个AS事件构建了一个SFs-AS网络。我们确定了结肠癌的11 AS标志。该特征可被视为独立的预后因素。从结肠癌样本中鉴定出2132例与生存相关的AS事件。我们开发了11个AS签名，其中5年AUC值为0.911。同时，在测试和整个队列中，五年的AUC值分别为0.782和0.855。多元Cox回归显示，T类别和签名风险分数是结肠癌生存的独立风险因素。此外，我们基于11个SF和48个AS事件构建了一个SFs-AS网络。我们确定了结肠癌的11 AS标志。该特征可被视为独立的预后因素。从结肠癌样本中鉴定出2132例与生存相关的AS事件。我们开发了11个AS签名，其中5年AUC值为0.911。同时，在测试和整个队列中，五年的AUC值分别为0.782和0.855。多元Cox回归显示，T类别和签名风险分数是结肠癌生存的独立风险因素。此外，我们基于11个SF和48个AS事件构建了一个SFs-AS网络。我们确定了结肠癌的11 AS标志。该特征可被视为独立的预后因素。多元Cox回归显示，T类别和签名风险分数是结肠癌生存的独立风险因素。此外，我们基于11个SF和48个AS事件构建了一个SFs-AS网络。我们确定了结肠癌的11 AS标志。该特征可被视为独立的预后因素。多元Cox回归显示，T类别和签名风险分数是结肠癌生存的独立风险因素。此外，我们基于11个SF和48个AS事件构建了一个SFs-AS网络。我们确定了结肠癌的11 AS标志。该特征可被视为独立的预后因素。