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BackgroundAlternative splicing (AS) is a molecular event that drives protein diversity by generating multiple mRNA isoforms. Increasing evidence shows that the differential expression of AS is related to tumorigenesis. However, a synthetic analysis for identifying the AS biomarkers attributed to glioblastoma (GBM) is mostly unexplored. MethodsAS percent-splice-in (PSI) data were obtained from the TCGA SpliceSeq database. We systematically and interactively analyzed differentially expressed alternative splicing (DEAS) events in GBM. Univariate and multivariate Cox regression analysis was successively performed to identify the overall survival (OS)-associated DEAS events, followed by the construction of DEAS predictor through different splicing patterns. Then, a nomogram that combines the final DEAS predictor and clinicopathological characteristics was established. Finally, a splicing regulatory network was created according to the correlation between the DEAS events and the splicing factors (SF). Summary illustrations show Figure1.ResultsA total of 2697 DEAS events detected in 2206 gene symbols consisted of 1054 upregulated DEAS events and 1643 downregulated DEAS events. Notably, these DEAS events are mainly involved in neuron-synapse signaling and metabolism-related processes in GBM. We identified 135 DEAS events that were substantially associated with the overall survival of GBM patients; for example, the alternate promoter (AP) of GSG1L and alternate terminator (AT) of CDKL3 were associated with poor prognosis, whereas AP of TMEM63, exon skip (ES) of CPEB4, AT of FAM13A, AT of OBSL1, AT of HNF1A, and AT of CCDC40 were associated with good prognosis. Following this, we constructed a potential splicing factor (SF)-AS regulatory network and identified nine key SFs, including ELAVL4, CELF3, CELF5, RBFOX1, YWHAH, STXBP1, CELF4, ELAVL2, and DNM1, which are mainly involved in RNA metabolism and insulin synthesis. ConclusionsIn summary, we demonstrated the role of DEAS events in the progression of GBM, providing a potential clinical biomarker and therapeutic reference for GBM. |
