Identification of an autophagy-related prognostic signature in head neck squamous cell carcinoma

Abstract Background Autophagy-related genes (ARGs) have been significantly implicated in tumorigenesis and served as promising prognostic biomarkers for human cancer. Hence, this study was aimed to develop an ARGs-based prognostic signature for head neck squamous cell carcinoma (HNSCC). Methods Prognostic ARG candidates were identified by univariate and multivariate Cox regression analysis in training set (TCGA-HNSC) and incorporated into a 3-ARGs (EGFR, FADD, PARK2) prognostic signature, which further verified in two independent validation cohorts (GSE41613 and GSE42743). Kaplan-Meier plots, Cox regression analyses and receiver operating characteristics curves (ROC) were employed to evaluate the prognostic prediction of 3-ARGs signature. Differential expression of these 3 ARG between cancer and normal counterparts as well as their associations with autophagy markers were assessed using Human Protein Profiles dataset. Results Patients with high-risk score had significantly inferior overall survival. Multivariate survival analyses revealed that 3-ARGs signature could be an independent prognostic factor. ROC analyses revealed the high predictive accuracy and sensitivity of 3-ARGs signature. Increased expression of EGFR, FADD, PARK2 were found in HNSCC samples and their expression significantly correlated with levels of ATG5, Beclin1 and LC3. Conclusions Our results reveal that 3-ARGs signature is a powerful prognostic biomarker for HNSCC, which could be integrated into current prognostic regime to realize individualized outcome prediction.