Comprehensive analysis of prognostic alternative splicing signature in cervical cancer
Comprehensive analysis of prognostic alternative splicing signature in cervical cancer
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DOI：
10.1186/s12935-020-01299-4
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发表时间：
2020-06-08
影响因子：
5.8
通讯作者：
Wang, Zehua
中科院分区：
文献类型：
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作者：
Ouyang, Dong;Yang, Ping;Wang, Zehua
选择性剪接（AS）是蛋白质编码基因多样性的关键因素，与恶性肿瘤的发生和进展有关。然而，AS在宫颈癌中的作用尚不清楚。方法从The Cancer Genome Atlas (TCGA) SpliceSeq网站下载宫颈鳞状细胞癌和宫颈内腺癌（CESC）的AS数据。通过单变量Cox分析，很少有预后性AS事件被确定。我们进一步确定了7种AS事件亚型的预后预测模型，并评估了它们的预测能力。我们通过对预后AS事件的全局分析构建了临床预测模型，并利用预后模型计算的风险评分和相关临床信息建立了nomogram。采用无监督聚类分析探讨模型中预后AS事件与临床特征之间的关系。结果共发现2860例宫颈癌AS预后事件。单一候补受体亚型预测效果最佳，曲线下面积为0.96。我们的临床预后模型包括一个9 - as事件特征，预测的nomogram模型的c指数为0.764。SNRPA和CCDC12是预后相关剪接因子的中心基因。通过9个预后AS事件的无监督聚类分析揭示了三个不同生存模式的聚类。结论sa事件影响宫颈癌的预后和生物学进展。已确定的AS预后事件和剪接调节网络可以增加我们对宫颈癌潜在机制的理解，提供新的治疗策略。
BackgroundAlternative splicing (AS) is a key factor in protein-coding gene diversity, and is associated with the development and progression of malignant tumours. However, the role of AS in cervical cancer is unclear.MethodsThe AS data for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) were downloaded from The Cancer Genome Atlas (TCGA) SpliceSeq website. Few prognostic AS events were identified through univariate Cox analysis. We further identified the prognostic prediction models of the seven subtypes of AS events and assessed their predictive power. We constructed a clinical prediction model through global analysis of prognostic AS events and established a nomogram using the risk score calculated from the prognostic model and relevant clinical information. Unsupervised cluster analysis was used to explore the relationship between prognostic AS events in the model and clinical features.ResultsA total of 2860 prognostic AS events in cervical cancer were identified. The best predictive effect was shown by a single alternate acceptor subtype with an area under the curve of 0.96. Our clinical prognostic model included a nine-AS event signature, and the c-index of the predicted nomogram model was 0.764. SNRPA and CCDC12 were hub genes for prognosis-associated splicing factors. Unsupervised cluster analysis through the nine prognostic AS events revealed three clusters with different survival patterns.ConclusionsAS events affect the prognosis and biological progression of cervical cancer. The identified prognostic AS events and splicing regulatory networks can increase our understanding of the underlying mechanisms of cervical cancer, providing new therapeutic strategies.