Identification of Prognostic alternative splicing signatures and their clinical significance in uveal melanoma

Abstract

As a posttranscriptional regulatory mechanism, alternative splicing (AS) has the potential to generate a large amount of protein diversity from limited genes. The purpose of our study was to assess the usefulness of prognostic splicing events as novel diagnostic and therapeutic signatures for uveal melanoma (UM). The datasets, clinical traits and AS data of UM were obtained from The Cancer Genome Atlas (TCGA) database and TCGA SpliceSeq database. Using bioinformatics analysis, we identified 1047 AS events as candidate AS events closely related to prognosis from 920 parent genes. The gene enrichment analysis indicated that these genes were mainly enriched in cellular components (CC) including cytosol, nucleoplasm, cytoplasm and ribosome, and in molecular functions (MF), including protein binding and poly(A) RNA binding. Furthermore, we selected all survival-associated splicing events to generate prognostic signatures, which included 4 exon skip (ES) events (DNASE1L1-90581-ES, NUDT1-78611-ES, BIN1-55198-ES, SEPN1-1195-ES) and 1 alternate promoter (AP) event (DPYSL2-83132-AP). The AS prognostic model was confirmed as independent overall survival (OS)-related factors (p = 0.014). A total of 17 splicing factors (SFs) involved in the regulation of AS were identified as related to the OS of UM patients. Our pooled data highlighted the usefulness and importance of AS biomarkers, which provided a potential strategy for the diagnosis and treatment of UM.