Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma.

Abstract

Glioblastoma (GBM) is the most aggressive malignant brain tumour, with high morbidity and mortality rates. Currently, there is a lack of systematic and comprehensive analysis on the prognostic significance of alternative splicing (AS) profiling for GBM. The GBM data, including RNA-sequencing, corresponding clinical information and the expression levels of splicing factor genes, were downloaded from The Cancer Genome Atlas and the SpliceAid2 database. The prognostic models were assessed by the least absolute shrinkage and selection operator Cox regression analysis. The correlation network between survival-associated AS events and splicing factors was plotted. Prognostic models were built for every AS event type and performed well for risk stratification in patients with GBM. The final prognostic signature served as an independent prognostic factor [hazard ratio (HR), 4.61; 95% confidence interval (CI), 2.97–7.16; P=9.66×10−12] for several clinical parameters, including age, sex, isocitrate dehydrogenase mutation, O6-methylguanine-DNA methyltransferase promoter methylation and risk score. The HR for risk score with GBM was 1.0063 (95% CI, 1.0024–1.0103). The splicing regulatory network indicated that heat shock protein b-1, protein arginine N-methyltransferase 5, protein FAM50B and endoplasmic reticulum chaperone BiP genes were independent prognostic factors for GBM. The results of the present study support the ongoing effort in developing novel genomic models and providing potentially more effective treatment options for patients with GBM.