Genome-Wide Profiling and Clinical Significance of Alternative Splicing Events in Glioblastoma

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Aims: </jats:bold>The purpose of this study was to depict alternative splicing (AS) profiles in GBM and identify their clinical significance in the progression of GBM. <jats:bold>Materials and Methods:</jats:bold> RNA sequence data and clinical information were downloaded from The Cancer Genome Atlas portal (https://portal.gdc.cancer.gov/projects). Genome-wide alternative splicing events were obtained using SpliceSeq tool. Analyses were performed using GraphPad Prism 7 and R software. <jats:bold>Key findings: </jats:bold>Univariate Cox analysis identified 2406 AS events with prognostic significance. We built an interaction network based on these survival-related AS events. Unsupervised clustering analysis showed that patients in cluster 2 had a better prognosis than those in other clusters. The prognostic splicing factors and AS events were used to generate a splicing network. Seven prognostic signatures, developed based on the top three survival-related AS events, predicted the survival risk and may serve as independent indicators of unfavorable prognosis. Among these risk signatures, only the alternate promoter (AP) signature was upregulated in the mesenchymal subtype, which is characterized by a complex immune microenvironment. A high AP risk score indicated an overloaded local immune response and enriched immune cell infiltration, which may accelerate the progression of GBM.<jats:bold>Significance:</jats:bold> AS-related signatures may serve as predictors of prognosis as well as provide treatment targets and guidance for GBM patients.</jats:p>