Prognostic Significance of SASP-Related Gene Signature of Radiation Therapy in Head and Neck Squamous Cell Carcinoma

Abstract In this study, we developed and validated the clinical significance of senescence-associated secretory phenotype (SASP)-related gene signature and explored its association with radiation therapy (RT) in patients with head and neck squamous cell carcinoma (HNSCC). First, we searched the three published review literature associated with SASP and selected all 81 genes to develop SASP-related gene signature. Then, 81 SASP-related genes were adapted to gene expression dataset from The Cancer Genome Atlas (TCGA). Patients with HNSCC of TCGA were classified into clusters 1 and 2 via unsupervised clustering according to SASP-related gene signature. Kaplan–Meier plot survival analysis showed that cluster 1 had a poorer prognosis than cluster 2 in 5-year overall survival and recurrence-free survival. Similarly, cluster 1 showed a worse prognosis than cluster 2 in three validation cohorts (E-MTAB-8588, FHCRC, and KHU). Cox proportional hazards regression observed that the SASP-related signature was an independent prognostic factor for patients with HNSCC. We also established a nomogram using a relevant clinical parameter and a risk score. Time-dependent receiver operating characteristic analysis was carried out to assess the accuracy of the prognostic risk model and nomogram. Senescence SASP-related gene signature was associated with the response to RT. Therefore, subsequent, in vitro experiments further validated the association between SASP-related gene signature and RT in HNSCC. In conclusion, we developed a SASP-related gene signature, which could predict survival of patients with HNSCC, and this gene signature provides new clinical evidence for the accurate diagnosis and targeted RT of HNSCC.