Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China.
Chengdu Foreign Language School, Chengdu, China.
J Cell Mol Med. 2019 Nov;23(11):7762-7772. doi: 10.1111/jcmm.14651. Epub 2019 Sep 5.
Alternative splicing (AS) contributes to protein diversity by modifying most gene transcriptions. Cancer generation and progression are associated with specific splicing events. However, AS signature in kidney renal clear cell carcinoma (KIRC) remains unknown. In this study, genome-wide AS profiles were generated in 537 patients with KIRC in the cancer genome atlas. With a total of 42 522 mRNA AS events in 10 600 genes acquired, 8164 AS events were significantly associated with the survival of patients with KIRC. Logistic regression analysis of the least absolute shrinkage and selection operator was conducted to identify an optimized multivariate prognostic predicting mode containing four predictors. In this model, the receptor-operator characteristic curves of the training set were built, and the areas under the curves (AUCs) at different times were >0.88, thus indicating a stable and powerful ability in distinguishing patients' outcome. Similarly, the AUCs of the test set at different times were >0.73, verifying the results of the training set. Correlation and gene ontology analyses revealed some potential functions of prognostic AS events. This study provided an optimized survival-predicting model and promising data resources for future in-depth studies on AS mechanisms in KIRC.
可变剪接(AS)通过修饰大多数基因转录来增加蛋白质的多样性。癌症的发生和发展与特定的剪接事件有关。然而,肾透明细胞癌(KIRC)中的 AS 特征尚不清楚。在这项研究中,癌症基因组图谱中对 537 名 KIRC 患者进行了全基因组 AS 谱分析。共获得 10600 个基因中的 42522 个 mRNA AS 事件,其中 8164 个 AS 事件与 KIRC 患者的生存显著相关。采用最小绝对收缩和选择算子的逻辑回归分析,确定了一个包含四个预测因子的优化多变量预后预测模型。在该模型中,构建了训练集的接收器工作特征曲线,不同时间的曲线下面积(AUC)均>0.88,表明其在区分患者预后方面具有稳定而强大的能力。同样,不同时间测试集的 AUC>0.73,验证了训练集的结果。相关性和基因本体分析揭示了一些预后 AS 事件的潜在功能。该研究为 KIRC 中 AS 机制的深入研究提供了一个优化的生存预测模型和有前途的数据资源。