Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Gastrointestinal Pan-Adenocarcinomas.
Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Gastrointestinal Pan-Adenocarcinomas.
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DOI：
10.1016/j.ebiom.2018.07.040
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发表时间：
2018-08
期刊：
影响因子：
11.1
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Lin P;He RQ;Ma FC;Liang L;He Y;Yang H;Dang YW;Chen G
胃肠道全腺癌主要包括食管、胃、结肠和直肠的腺癌，由于其预后差，给社会带来了沉重的负担。由于异常选择性剪接（AS）开始被认为是预测肿瘤预后和治疗靶点的有效标志，因此对AS事件的系统分析是迫切的。采用单因素考克斯回归分析筛选与预后相关的AS事件。基因功能富集分析揭示了AS相关基因富集的途径。然后，基于AS事件的预后特征被开发用于预后预测。通过Pearson相关分析了剪接因子调控剪接事件的可能机制，构建了剪接调控网络。在食管、胃、结肠和直肠腺癌中，分别有967、918、674和406例AS事件被确定为肿瘤相关AS事件。生存相关的AS事件在腺癌的四个亚型中是有区别的。此外，计算算法的结果表明，核糖体和泛素介导的蛋白质水解途径的扰动是潜在的分子机制，对应于劣质啤酒。最值得注意的是，基于AS事件的几个预后标志在预后预测中显示出中等的性能。食管癌、胃癌、结肠癌和直肠癌的时间依赖性受试者工作特征曲线下的面积分别为0.961、0.871、0.870和0.890。生存相关的剪接因子被提交来构建AS调控网络，这可能是AS事件的潜在机制。AS可能是胃肠道全腺癌预后的理想指标。探索有趣的剪接调控网络有助于解决AS的难题。
Gastrointestinal pan-adenocarcinomas, which mainly include adenocarcinomas of the esophagus, stomach, colon, and rectum, place a heavy burden on society owing to their poor prognoses. Since aberrant alternative splicing (AS) are starting to be considered as efficacious signatures for tumor prognosis predicting and therapeutic targets, systematic analysis of AS events is urgent. Prognosis-related AS events were selected by using univariate COX regression analysis. Gene functional enrichment analysis revealed the pathways enriched by prognosis-related AS. Then, prognostic signatures based on AS events were developed for prognosis prediction. Potential mechanism to regulate splicing events by splicing factors was analyzed via Pearson correlation and regulatory networks were constructed. A total of 967, 918, 674, and 406 AS events were identified as prognosis-related AS events in esophagus, stomach, colon, and rectum adenocarcinomas, respectively. Survival-associated AS events were distinguishing in the four subtypes of adenocarcinoma. Furthermore, computational algorithm results indicated that perturbation of ribosome and ubiquitin-mediated proteolysis pathways were the potential molecular mechanisms corresponding to inferior prognoses. Most notably, several prognostic signatures based on AS events displayed moderate performance in prognosis predicting. The area under curve values of the time-dependent receiver operating characteristic were 0.961, 0.871, 0.870, and 0.890 in esophagus, stomach, colon, and rectum adenocarcinomas. Survival-associated splicing factors were submitted to construct the AS regulatory network, which could be an underlying mechanism of AS events. AS may could be ideal indiactors in the prognosis of gastrointestinal pan-adenocarcinomas. Exploring interesting splicing regulatory networks is conducive to solve the puzzles of AS.
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