Identification of Prognostic Alternative Splicing Signature in Triple-negative breast cancer

Abstract Background: Alternative splicing (AS) is a pervasive and vital mechanism involved in the progression of various cancer. Studies confirm the importance of prognostic value of AS events in tumor patients, but systematic analysis of AS in triple-negative breast cancer (TNBC) is still lacking. Methods: Information from 115 TNBC patients from the Cancer Genome Atlas (TCGA) database were extracted. And we performed a comprehensive analysis of whole-genome AS events with corresponding clinical information to evaluate the roles of seven AS patterns. Prognostic analyses were performed with predictive models and splicing network built for TNBC patients. Results: Among 28,744 mRNA AS events in 20,353 genes, we detected 1,428 AS in 138 important survival genes related to the overall survival of TNBC patients event. Through functional and pathway enrichment analysis, we found that these genes are involved in ubiquitin-mediated proteolytic pathways. At 1800 days overall survival, the area under the ROC curve for prognostic signatures was 0.8. It shows that this model is very effective in differentiating patient prognosis. The use of Spearman's test to establish a potential regulatory network between survival-related AS events and abnormal SF indicates a clear trend in the role of SF in TNBC. Conclusions: In summary, we established a reliable and powerful TNBC prognostic signature. A splicing network that could be its underlying mechanism was discovered. Keywords: Alternative splicing; Triple-negative breast cancer; Prognosis; Splicing factor