Profiles of alternative splicing landscape in breast cancer and their clinical significance: an integrative analysis based on large-sequencing data.

Background: Alternative splicing (AS) is closely correlated with the initiation and progression of carcinoma. The systematic analysis of its biological and clinical significance in breast cancer (BRCA) is, however, lacking.

Methods: Clinical data and RNA-seq were obtained from the TCGA dataset and differentially expressed AS (DEAS) events between tumor and paired normal BRCA tissues were identified. Enrichment analysis was then used to reveal the potential biological functions of DEAS events. We performed protein-protein interaction (PPI) analysis of DEAS events by using STRING and the correlation network between splicing factors (SFs) and AS events was constructed. The LASSO Cox model, Kaplan-Meier and log-rank tests were used to construct and evaluate DEAS-related risk signature, and the association between DEAS events and clinicopathological features were then analyzed.

Results: After strict filtering, 35,367 AS events and 973 DEAS events were detected. DEAS corresponding genes were significantly enriched in pivotal pathways including cell adhesion, cytoskeleton organization, and extracellular matrix organization. A total of 103 DEAS events were correlated with disease free survival. The DEAS-related risk signature stratified BRCA patients into two groups and the area under curve (AUC) was 0.754. Moreover, patients in the high-risk group had enriched basel-like subtype, advanced clinical stages, proliferation, and metastasis potency.

Conclusions: Collectively, the profile of DEAS landscape in BRCA revealed the potential biological function and prognostic value of DEAS events.