Development of a Prognostic Signature Based on Autophagy-related Genes for Head and Neck Squamous Cell Carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor with relative low survival rate. Increasingly evidences have emphasized the importance of autophagy in cancer initiation, progression, and the responses to cancer treatment. This study aimed to investigate the potential biological and prognostic significance of autophagy-related genes (ARGs) in HNSCC patients. We collected a list of ARGs from Human Autophagy Database and obtained expression profiles and clinical information of HNSCC samples from the Cancer Genome Atlas (TCGA) portal. Differential expression analysis and functional enrichment analysis were performed by R software. The prognostic value of differentially expressed ARGs was detected by Cox regression analysis and prognosis-related ARGs were subjected to LASSO regression analysis. Univariate and multivariate Cox regression analysis were applied to identify promising independent prognosticators for HNSCC. A total of 35 differentially expressed ARGs were screened out and functional enrichment analysis results indicated these genes were mainly associated with autophagy-related biological processes and pathways. Seven prognosis-related ARGs (ITGA3, CDKN2A, FADD, NKX2-3, BAK1, CXCR4, and HSPB8) were selected to construct a risk signature, which proved to be effective in predicting the survival rate of HNSCC patients. Moreover, univariate analysis showed risk score, tumor stage, T stage, and N stage were negatively correlated with patient overall survival and the multivariate Cox regression analysis results indicated risk score, age, and N stage was significantly associated with patient prognosis. Our findings may provide novel evidences for the diagnosis and prognosis evaluation for HNSCC.