Abstract
Due to limitations of sensitive biomarkers, the clinical prognosis of patients with head and neck squamous cell carcinoma (HNSCC) remains poor. Alternative splicing (AS) is the basis of both transcriptome and proteome richness, so more and more evidence indicates an important relationship between AS and tumor progression. The aim of this study was to offer a comprehensive analysis on AS events and then investigate its potentials as a new biomarker for patients with squamous cell carcinoma of the head and neck. In this study, univariate assays were conducted to examine the prognosis-associated AS events, and we screened 4068 survival-related AS events in 2573 genes. Then, the AS events related to survival were further determined and analyzed using LASSO regression and multivariate assays, and an eleven-AS signature was developed. Kaplan–Meier assays indicated patients with high-risk scores exhibited a shorter OS than those with low-risk scores. Multivariate assays further demonstrated that the signature's risk score was independent of HNSCC survivals. Meanwhile, we analyzed the clinical association of AS-based prognostic signature in HNSCC patients and observed that tumor specimens with advanced stages and grades exhibited a high risk score. In addition, the results of survival nomogram revealed that predicted outcomes and actual outcomes were highly consistent. Overall, our group showed an eleven-AS signature of HNSCC, which could be regarded as a separate prognostic factor.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the epidermis of the head and neck, involving multiple anatomical sites, such as the lip, oral cavity, pharynx, and larynx, and more than 600,000 new cases are reported every year [1, 2]
After excluding Alternative splicing (AS) events with SD
To screen the final AS events for prognostic model, the overall survival (OS)-related AS events were analyzed by using lasso analysis. en, multivariate assays were applied to analyze the results of lasso analysis via the forward stepwise methods
Summary
Head and neck squamous cell carcinoma (HNSCC) is the most common malignant tumor of the epidermis of the head and neck, involving multiple anatomical sites, such as the lip, oral cavity, pharynx (nasopharynx, oropharynx, and hypopharynx), and larynx, and more than 600,000 new cases are reported every year [1, 2]. Alternative splicing (AS) is considered to be a critical impetus for the production of different types of proteins [5]. In eukaryotic cells, it is the basis for the other regulatory mechanisms involved in gene functions. On the other hand, targeting AS events may be developed as novel therapeutic targets for tumor patients. A large number of studies have performed comprehensive analysis based on TCGA splicing data in several types of tumors [14, 15]. There are very few reports on the correlation between AS events and the clinical outcomes of HNSCC patients. A comprehensive analysis was performed by using TCGA datasets to discuss the prognostic value of AS events in patients with HNSCC. Our findings may contribute to the developments of novel biomarkers for tumor patients
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