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The results confirmed that high expression of SPNS2 and SPNS3 were poor prognostic factors, and the effect of SPNS2 can be neutralized by allo-HSCT.Increasing evidence has demonstrated that changes in alternative splicing (AS) events are closely associated with the initiation and progression of cancer. However, the concrete role of AS in tumorigenesis of head and neck squamous cell carcinoma (HNSCC) is poorly known. In this study, we aimed to investigate the AS profile in HNSCC, and build up a robust AS-based prognostic signature for HNSCC. Our results reve