Wei Chunyin, Xie Weishun, Huang Xiaoliang, Mo Xianwei, Liu Zujun, Wu Guo, Meng Yongsheng, Jeen Franco, Ge Lianying, Zhang Lihua, Liao Lixian, Liu Jungang, Tang Weizhong
Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
J Cancer. 2021 Mar 19;12(10):2982-2992. doi: 10.7150/jca.46239. eCollection 2021.
Gastric cancer (GC) is a heterogeneous disease, and alternative splicing (AS) is a powerful universal transcriptional regulatory mechanism that contributes to the occurrence and development of cancer. However, the systematic analysis of AS events in GC is lacking; therefore, further studies are needed. Genome-wide analysis of AS events was performed using RNA-Seq data to evaluate the difference between GC and adjacent tissues at the AS level. Prognostic signatures based on differentially expressed alternative splicing (DEAS) events and a correlation network between DEAS and genes were built. We identified 48,141 AS events, of which 2325 showed differential expression patterns. The parental genes before DEAS events play an essential role in regulating GC-related processes such as ribosome (FDR < 0.0001) and thermogenesis (FDR = 0.0002). There were 76 survival-associated DEAS cases. Stratifying patients according to the percent spliced in index value of six types of splicing patterns formed significant Kaplan-Meier curves in the overall survival analysis. A prognostic feature based on DEAS performed well for stratification in patients with GC. The present study will enrich our understanding regarding the distinction of GC and provide a generous amount of biomarkers and potential targets for the treatment of GC.
胃癌（GC）是一种异质性疾病，而可变剪接（AS）是一种强大的普遍转录调控机制，与癌症的发生和发展有关。然而，目前缺乏对GC中AS事件的系统分析，因此需要进一步研究。利用RNA测序数据对AS事件进行全基因组分析，以评估GC组织与相邻组织在AS水平上的差异。构建了基于差异表达可变剪接（DEAS）事件的预后特征以及DEAS与基因之间的相关网络。我们共鉴定出48141个AS事件，其中2325个表现出差异表达模式。DEAS事件之前的亲本基因在调节与GC相关的过程中起着重要作用，如核糖体（FDR < 0.0001）和产热（FDR = 0.0002）。有76个与生存相关的DEAS病例。在总生存分析中，根据六种剪接模式的剪接百分率指数值对患者进行分层，形成了显著的Kaplan-Meier曲线。基于DEAS的预后特征在GC患者分层中表现良好。本研究将丰富我们对GC差异的理解，并为GC治疗提供大量生物标志物和潜在靶点。
