Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Med Oncol. 2021 Mar 27;38(5):49. doi: 10.1007/s12032-021-01490-1.
Increasing evidence demonstrated that alternative splicing (AS) plays a vital role in tumorigenesis and clinical outcome of patient. However, systematical analysis of AS in lung squamous cell carcinoma (LUSC) is lacking and greatly necessary. Thus, this study was to systematically estimate the function of AS events served as prognostic indicators in LUSC. Among 31,345 mRNA AS events in 9633 genes, we detected 1996 AS in 1409 genes which have significant connection with overall survival (OS) of LUSC patients. Then, prognostic model based on seven types of AS events was established and we further constructed a combined prognostic model. The Kaplan-Meier curve results suggested that seven types of AS signatures and the combined prognostic model could exhibit robust performance in predicting prognosis. Patients in the high-risk group had significantly shorter OS than those in the low-risk group. The ROC showed all prognostic models had high accuracy and powerful predictive performance with different AUC ranging from 0.837 to 0.978. Moreover, the combined prognostic model had highest performance in risk stratification and predictive accuracy than single prognostic models and had higher accuracy than other mRNA model. Finally, a significant correlation network between survival-related AS genes and prognostic splicing factors (SFs) was established. In conclusion, our study provided several potential prognostic AS models and constructed splicing network between AS and SFs in LUSC, which could be used as potential indicators and treatment targets for LUSC patients.
越来越多的证据表明，可变剪接（AS）在肿瘤发生和患者临床结局中起着至关重要的作用。然而，系统分析肺鳞状细胞癌（LUSC）中的 AS 仍然缺乏，且非常有必要。因此，本研究旨在系统评估作为 LUSC 预后指标的 AS 事件的功能。在 9633 个基因的 31345 个 mRNA AS 事件中，我们检测到 1409 个基因中的 1996 个 AS 与 LUSC 患者的总生存期（OS）有显著关联。然后，基于七种类型的 AS 事件建立了预后模型，我们进一步构建了一个组合预后模型。Kaplan-Meier 曲线结果表明，七种类型的 AS 特征和组合预后模型可以在预测预后方面表现出稳健的性能。高风险组的患者 OS 明显短于低风险组。ROC 显示所有预后模型均具有较高的准确性和强大的预测性能，不同 AUC 范围从 0.837 到 0.978。此外，与单预后模型相比，组合预后模型在风险分层和预测准确性方面表现出更高的性能，且准确性高于其他 mRNA 模型。最后，建立了生存相关 AS 基因与预后剪接因子（SFs）之间的显著相关网络。总之，本研究提供了几个潜在的预后 AS 模型，并构建了 LUSC 中 AS 与 SFs 之间的剪接网络，可作为 LUSC 患者的潜在指标和治疗靶点。
