Genome-Wide Profiling of Prognostic Alternative Splicing Pattern in Pancreatic Cancer

Background: Increasing evidence has also demonstrated that Alternative splicing (AS) has a critical role on tumor progression and prognosis. However, the scarcity of studies undertakes a comprehensive examination of survival associated AS events in pancreatic cancer. The aim of our study to explore pancreatic cancer-specific AS events using RNA-seq data, gaining systematic insights into potential functions served as prognostic biomarkers.   Methods: We downloaded RNA-Seq data of the PAAD cohort from the TCGA database. Then univariate and multivariate Cox regression analyses and were performed to identify survival-related AS events in pancreatic cancer assessed by receiver operator characteristic curves (ROC). Cytoscape was also used to depict function annotation, pathway enrichment and gene interaction network on survival-related AS genes. Finally, Pearson's correlation test was applied to assess the association between survival-related AS and survival-related splicing factors, while investigating the association between expression of driver genes and AS events.   Findings: In total, 10623 genes with 45313 AS events were detected in 178 pancreatic samples. Cox univariate analyses of overall survival suggested 6711 AS events significantly associated with patient overall survival (P<0.05). The area under the curves of the ROC of risk score was 0.89 for final prognostic. Splicing network also demonstrated significant connection between the expression of splicing factors and AS events in PAAD patients.   Interpretation: Our comprehensive investigation first focused on the aberrant AS patterns in pancreatic cancer which might serve as prognostic predictors.   Funding Statement: This study was supported by grants from National Natural Science Foundation of China (Grant No. 81701560).  This funding made significant contribution to study design, data interpretation and writing. Declaration of Interests: The authors state that they have no conflicts of interest. Ethics Approval Statement: The authors declare: "This article does not contain any studies with animals performed by any of the authors."