Research Paper Volume 12, Issue 21 pp 21923—21941
Prognostic significance of survival-associated alternative splicing events in gastric cancer
- 1 Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, Guizhou, P.R. China
- 2 Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education of China, Guiyang 550025, Guizhou, P.R. China
- 3 Affiliated Tumor Hospital, Guizhou Medical University, Guiyang 550025, Guizhou, P.R. China
- 4 The Clinical Laboratory of Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China
Received: March 4, 2020 Accepted: August 17, 2020 Published: November 7, 2020
https://doi.org/10.18632/aging.104013How to Cite
Copyright: © 2020 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Alternative splicing events are a major source of transcript and protein diversity in eukaryotes. Aberrant alternative splicing events have been increasingly reported in various cancers, including gastric cancer. To further explore the prognostic significance of alternative splicing events in gastric cancer patients, a comprehensive and systematic investigation was conducted by integrating alternative splicing event data and clinical information. Univariate Cox regression analysis identified 1383 alternative splicing events to be significantly associated with the overall survival of gastric cancer patients. Then, least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were performed for the development of prognostic signatures. The final prognostic signature based on all seven types of alternative splicing events can act as an independent prognostic indicator after multivariate adjustment of several clinical parameters. Furthermore, the correlation and function analysis identified CELF2, BAG2, RBFOX2, PTBP2 and QKI as hub splicing factors, and the focal adhesion signaling pathway was most significantly correlated with survival-associated alternative splicing events. The results of this study may establish a foundation for further research investigating the underlying mechanism of alternative splicing events in the progression of gastric cancer.
Abbreviations
GC: gastric cancer; AS: alternative splicing; ES: exon skip; RI: retained intron; AD: alternate donor site; AA: alternate acceptor site; AP: alternate promoter; AT: alternate terminator; ME: mutually exclusive exons; TCGA: The Cancer Genome Atlas; LASSO: least absolute shrinkage and selection operator; ROC: receiver operating characteristic; AUC: area under the ROC curve; PSI: percent spliced in; HR: hazard ratio; CI: confidence interval; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes.