Wang Zhiwu, Wu Qiong, Liu Yankun, Li Qingke, Li Jingwu
Department of Chemoradiotherapy, Tangshan People`S Hospital, Tangshan, China.
The Cancer Institute, Tangshan People's Hospital, Tangshan, 063001, China.
Arch Public Health. 2022 May 25;80(1):145. doi: 10.1186/s13690-022-00894-3.
Aberrant alternative splicing (AS) events could be viewed as prognostic indicators in a large number of malignancies. This study aims to identify prognostic AS events, illuminate the function of the splicing variants biomarkers and provide reliable evidence for formulating public health strategies for gastric cancer (GC) surveillance.
RNA-Seq data, clinical information and percent spliced in (PSI) values were available in The cancer genome atlas (TCGA) and TCGA SpliceSeq data portal. A three-step regression method was conducted to identify prognostic AS events and construct multi-AS-based signatures. The associations between prognostic AS events and splicing factors were also investigated.
We identified a total of 1,318 survival-related AS events in GC, parent genes of which were implicated in numerous oncogenic pathways. The final prognostic signatures stratified by seven types of AS events or not stratified performed well in risk prediction for GC patients. Moreover, five signatures based on AA, AD, AT, ES and RI events function as independent prognostic indicators after multivariate adjustment of other clinical variables. Splicing network also showed marked correlation between the expression of splicing factors and PSI value of AS events in GC patients.
Our findings provide a landscape of AS events and regulatory network in GC, indicating that AS events might serve as prognostic biomarkers and therapeutic targets for GC.
异常可变剪接（AS）事件可被视为大量恶性肿瘤的预后指标。本研究旨在识别预后性AS事件，阐明剪接变异体生物标志物的功能，并为制定胃癌（GC）监测的公共卫生策略提供可靠依据。
可从癌症基因组图谱（TCGA）和TCGA SpliceSeq数据门户获取RNA测序数据、临床信息和剪接百分率（PSI）值。采用三步回归法识别预后性AS事件并构建基于多AS的特征。还研究了预后性AS事件与剪接因子之间的关联。
我们在GC中总共鉴定出1318个与生存相关的AS事件，其亲本基因涉及众多致癌途径。由七种类型的AS事件分层或未分层的最终预后特征在GC患者的风险预测中表现良好。此外，基于AA、AD、AT、ES和RI事件的五个特征在对其他临床变量进行多变量调整后可作为独立的预后指标。剪接网络还显示GC患者中剪接因子的表达与AS事件的PSI值之间存在显著相关性。
我们的研究结果提供了GC中AS事件和调控网络的概况，表明AS事件可能作为GC的预后生物标志物和治疗靶点。
