J Cancer 2020; 11(15):4571-4580. doi:10.7150/jca.44746

Research Paper

Identification and validation of an alternative splicing-based prognostic signature for head and neck squamous cell carcinoma

Xinyuan Zhao1*✉, Shanshan Si1*, Xiaona Li1, Wenjuan Sun2, Li Cui3✉

1. Stomatological Hospital, Southern Medical University, Guangzhou 510280, China.
2. Department of Stomatology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.
3. UCLA School of Dentistry, Los Angeles, CA 90095, USA.
*Equal contribution

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Citation:
Zhao X, Si S, Li X, Sun W, Cui L. Identification and validation of an alternative splicing-based prognostic signature for head and neck squamous cell carcinoma. J Cancer 2020; 11(15):4571-4580. doi:10.7150/jca.44746. Available from http://www.jcancer.org/v11p4571.htm

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Abstract

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 revealed a total of 4068 overall survival (OS) associated AS events in the TCGA HNSCC cohort. The whole TCGA HNSCC cohort was randomly divided into discovery cohort and validation cohort. A prognostic signature including five AS events was developed with the discovery cohort based on the most significant OS-associated AS events. Then it was further successfully validated in the validation cohort. The AS-based risk signature was an independent prognostic indicator in both discovery cohort and validation cohort. This prognostic signature-based nomogram model showed excellent performance for predicting the OS of HNSCC. Splicing network analysis have identified the most correlated splicing factor-AS network in HNSCC. Collectively, we have constructed a robust AS-based prognostic signature which might contribute to improve the clinical outcome of HNSCC.

Keywords: prognostic signature, head and neck squamous cell carcinoma, survival analysis, alternative splicing events, splicing factor