A Novel Nomogram Combining Alternative Splicing Events and Clinical Factors for Prognosis Prediction in Head and Neck Squamous Cell Carcinoma

一种结合可变剪接事件和临床因素的新型列线图用于头颈部鳞状细胞癌的预后预测

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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.

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