Sixteen Cellular Senescence-associated DNA Methylation Signature Predicts Overall Survival in Patients with Head and Neck Squamous Cell Carcinoma

Objective: To construct a cellular senescence-related DNA methylation model to act as an independent prognosis predictor for patients with head and neck squamous cell carcinoma (HNSCC). Methods: Methylome, transcriptome and clinical information for 499 HNSCC patients were received from The Cancer Genome Atlas (TCGA) as a training set. An extra independent methylation dataset of 54 patients with oral squamous cell carcinoma (OSCC) was downloaded from the NCBI Gene Expression Omnibus (GEO) database as the validation set. To assess the cellular senescence level of each sample, the senescence score (SS) of each patient was calculated using the transcriptome data via single-sample gene set enrichment analysis (ssGSEA). Least absolute shrinkage and selection operator (LASSO) Cox regression analyses were conducted to confirm Cytosine, phosphoric acid and Guanine (CpG) sites for the development of a cellular senescence-related DNA methylation signature. Results: Based on the SS of each HNSCC patient in the TCGA cohort, the patients were divided into high-and low-SS subgroups. The high-SS group showed a better prognosis than the low-SS group. Moreover, 3,261 differentially methylated CpG sites (DMCs) were confirmed between the two groups. Among them, 16 DMCs were included to develop a 16-DNA methylation signature for evaluation of HNSCC prognosis using LASSO and multivariate Cox regression analysis. Conclusion: A novel cellular senescence-related 16-DNA methylation signature was determined, which can be used as an independent index to evaluate the prognosis of HNSCC patients and select appropriate treatment strategies.