J Cancer 2021; 12(10):2982-2992. doi:10.7150/jca.46239 This issue Cite
Research Paper
1. Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
2. Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
3. Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
*These authors contributed equally to this work.
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: alternative splicing, prognostic signature, gastric cancer, survival, TCGA