Abstract
BackgroundAberrant alternative splicing (AS) is implicated in biological processes of cancer. This study aims to reveal prognostic AS events and signatures that may serve as prognostic predictors for head and neck squamous cell carcinoma (HNSCC).MethodsPrognostic AS events in HNSCC were identified by univariate COX analysis. Prognostic signatures comprising prognostic AS events were constructed for prognosis prediction in patients with HNSCC. The correlation between the percent spliced in (PSI) values of AS events and the expression of splicing factors (SFs) was analyzed by Pearson correlation analysis. Gene functional annotation analysis was performed to reveal pathways in which prognostic AS is enriched.ResultsA total of 27,611 AS events in 15,873 genes were observed, and there were 3433 AS events in 2624 genes significantly associated with overall survival (OS) for HNSCC. Moreover, we found that AS prognostic signatures could accurately predict HNSCC prognosis. SF-AS regulatory networks were constructed according to the correlation between PSI values of AS events and the expression levels of SFs.ConclusionsOur study identified prognostic AS events and signatures. Furthermore, it established SF-AS networks in HNSCC that were valuable in predicting the prognosis of patients with HNSCC and elucidating the regulatory mechanisms underlying AS in HNSCC.
Highlights
Aberrant alternative splicing (AS) is implicated in biological processes of cancer
Profiles of alternative splicing events in head and neck squamous cell carcinoma (HNSCC) We processed The Cancer Genome Atlas (TCGA) splice-seq data and clinical information of a HNSCC cohort in TCGA, and a total of 347 patients were included in the analysis
27,611 AS events in 15,873 mRNAs were observed in HNSCC, indicating that AS events are common in the development of HNSCC
Summary
Aberrant alternative splicing (AS) is implicated in biological processes of cancer. Alternative splicing (AS) is a crucial posttranscriptional biological process that facilitates transcript variants and reprogramming of protein diversity in cells [1]. HNSCC is the sixth most common malignancy globally, and remains one of the leading causes of cancer-related death [9]. About half of the patients will develop locoregional recurrence or metastasis, and their five-year survival rates remains unsatisfactory [11]. These facts highlight the urgent need to identify underlying molecular mechanisms to develop effective therapy and improve the overall survival of patients
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