Survival associated alternative splicing events in diffuse large B-cell lymphoma

Growing evidence has revealed that the initiation of various malignancies is closely associated with alternative splicing (AS) events in certain key oncogenes. However, in diffuse large B-cell lymphoma (DLBCL), there is still a great deal to learn about AS variants. In this study, 33,724 AS variant profiles were obtained from 16,278 genes in 48 DLBCL cases. A total of 10 AS variants were identified as overall survival (OS)- related events via multivariate Cox regression analysis. Notably, alternative donor (AD) sites in AS events in the low-risk group showed a significantly better outcome in DLBCL patients than in the high risk group (P=0.0002). The area under the curve (AUC) of the receiver-operator characteristic curve (ROC) for ADs in DLBCL was 0.746. Furthermore, 66 related splicing factors were obtained to investigate their potential correlations with AS events. Factors SF1, HNRNPC, HNRNPD, and HNRNPH3 were significantly involved in different OS-related AS variants. Collectively, we constructed valuable prognostic predictors for DLBCL patients and mapped novel splicing networks for further investigation of the underlying mechanisms related to AS variants in DLBCLs.