Abstract
BackgroundAlternative splicing (AS) is reported to be related to the biological process of multiple malignancies. This study is conducted to identify survival-associated AS events and prognostic signatures that may serve as prognostic indicators for pancreatic cancer (PC).MethodsUnivariate Cox analysis was used to determine the survival-associated AS events in PC. Prognostic signatures were constructed by LASSO Cox analysis based on seven types of survival-associated AS events. The correlation between the expression of splicing factors (SFs) and the percent spliced in values of AS events was analyzed by Pearson correlation analysis. Risk scores were calculated to determine high- or low-risk patients with different types of AS events. Gene functional annotation analysis was performed to reveal pathways in which prognostic AS is enriched.ResultsA total of 45,313 AS events in 10,624 genes were observed, and there were 1,565 AS events in 1,223 genes significantly correlated with overall survival for PC. Kaplan–Meier analysis, receiver-operator characteristic curve, univariate and multivariate Cox analyses showed that AS prognostic signatures could effectively predict prognosis of patients with PC. Splicing factors–AS regulatory networks were established to demonstrate the interaction between AS events and SFs.ConclusionThe survival-associated AS events and prognostic signatures identified in this study can serve as useful tool for predicting prognosis of patients with PC. Moreover, the SF–AS regulatory networks may provide clues for the mechanisms underlying AS in PC.
Highlights
Alternative splicing (AS) is a crucial posttranscriptional biological process that is responsible for the modification of mRNA isoforms
After processing and integrating AS data from The Cancer Genome Atlas (TCGA) SpliceSeq, and gene expression and clinical data from TCGA-pancreatic adenocarcinoma (PAAD) dataset, and a total of 173 patients were included in the analysis
45,313 AS events in 10,624 mRNAs were observed in pancreatic cancer (PC), indicating that AS events are common in the development of PC
Summary
Alternative splicing (AS) is a crucial posttranscriptional biological process that is responsible for the modification of mRNA isoforms. RNA sequencing data generated by The Cancer Genome Atlas (TCGA) program facilitated the in-depth research to illustrate the profiling of AS. By collecting and analyzing RNA sequencing data from TCGA database, SpliceSeq (Ryan et al, 2016) provides processed data for the analysis of AS events in 33 types of cancers (Lin et al, 2018; Zhong et al, 2018; He et al, 2019). Alternative splicing (AS) is reported to be related to the biological process of multiple malignancies. This study is conducted to identify survival-associated AS events and prognostic signatures that may serve as prognostic indicators for pancreatic cancer (PC)
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