Genome-Wide Profiling of Alternative Splicing Signatures Associated with Prognosis and Immune Microenvironment of Hepatocellular Carcinoma

BACKGROUND The potential roles of alternative splicing (AS) in HCC remain unknown. This study aimed to identify AS signatures associated with the prognosis that influence the immune microenvironment of HCC. MATERIAL AND METHODS The SpliceSeq tool was employed for genome-wide profiling of 7 AS events in 361 HCC patients from The Cancer Genome Atlas (TCGA). A prognostic signature was built by integrating Cox regression and the least absolute shrinkage and selection operator (LASSO). The support vector machine (SVM) and receiver operating characteristic curve (ROC) were employed to analyze the AS events in the signatures to discriminate the immune microenvironment. RESULTS There were 3546 AS events highly linked to the survival of patients with HCC. The AS signature could effectively stratify HCC patients. Clustering analysis revealed 3 different immune clusters characterized with significantly different prognoses and were significantly correlated with AS signatures. The AS events in the final prognostic signature classified the immune cluster with an average AUC of the ROC (0.88). Moreover, a potential regulatory network of splicing events in HCC is presented. CONCLUSIONS We established the prognostic signature based on AS, which can effectively stratify HCC patients and predict the immune subtypes. Moreover, novel RNA splicing patterns and splicing-regulatory networks involved in HCC were discovered.