Department of Medical Oncology, the Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
Department of Thoracic Surgery; The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266003, China.
Aging (Albany NY). 2020 Apr 13;12(7):5878-5893. doi: 10.18632/aging.102983.
Alternative splicing (AS) is fundamental to transcriptome and proteome richness, and data from recent studies suggested a critical association between AS and oncogenic processes. To date, no systematic analysis has been conducted on AS from the perspective of different sexes and subtypes in non-small-cell lung cancer (NSCLC). Thus, we integrated the information of NSCLC patients from The Cancer Genome Atlas (TCGA) and evaluated AS profiles from the perspectives of sex and subtype. Eventually, a total of 813 and 1020 AS events were found to be significantly related to the overall survival (OS) of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. Four prognostic prediction models performed well at 1, 3, and 5 years, with an area under the receiver operating characteristic (ROC) curve (AUC) greater than 0.75. Notably, we explored the upstream splicing factors (SFs) and downstream regulatory mechanisms of the OS-associated AS events and verified four differentially expressed alternative splicing (DEAS) events via qPCR. These findings can provide important guidance for subsequent studies. In addition, we also constructed nomograms to facilitate early screening by clinicians and to determine patient outcomes in NSCLC.
选择性剪接（AS）是转录组和蛋白质组丰富的基础，最近的研究数据表明 AS 与致癌过程之间存在着至关重要的联系。迄今为止，尚无针对非小细胞肺癌（NSCLC）不同性别和亚型的 AS 的系统分析。因此，我们整合了来自癌症基因组图谱（TCGA）的 NSCLC 患者信息，并从性别和亚型的角度评估了 AS 谱。最终，发现共有 813 个和 1020 个 AS 事件与肺腺癌（LUAD）和肺鳞癌（LUSC）患者的总生存期（OS）显著相关。四个预后预测模型在 1、3 和 5 年的表现良好，其接收者操作特征（ROC）曲线下面积（AUC）均大于 0.75。值得注意的是，我们探讨了与 OS 相关的 AS 事件的上游剪接因子（SF）和下游调控机制，并通过 qPCR 验证了四个差异表达的选择性剪接（DEAS）事件。这些发现可为后续研究提供重要指导。此外，我们还构建了列线图，以方便临床医生进行早期筛查，并确定 NSCLC 患者的预后。
