Comprehensive Characterization of the Prognosis Value of Alternative Splicing Events in Acute Myeloid Leukemia.

ABSTRACT

Increasing evidence have demonstrated that dysregulated alternative splicing (AS) events promoted tumor development and was correlated with worse prognosis in the context of certain malignancies. Nevertheless, a comprehensive examination of the prognosis role of AS events in acute myeloid leukemia (AML) has not yet been illuminated. In this study, univariate and multivariate Cox regression analysis were used to identify survival-related AS events and independent prognostic predictors. The interaction between splicing factors (SFs) and AS events was visualized by Cytoscape. A total of 3013 survival-associated AS events in 1977 genes were screened in 151 AML patients. Interestingly, the majority (2031 events) were revealed to be protective factors. Furthermore, the prediction models were constructed for each type of AS and all of them displayed good performance in predicting prognosis, considering their area under curve values of the receiver operating characteristic were all above 0.7. Notably, the splicing regulatory network displayed the underlying interaction networks between SFs and AS events. Taken together, our study demonstrated the survival-related AS events in AML and uncovered the possible association between SFs and prognostic AS events, which provide new prognostic biomarkers and aid to develop novel targets for AML therapy.