In this study, we initially performed a comprehensive investigation of the associations between 41 differentially expressed AGs (DEAGs, Figure 1A, 1B) and HNSCC prognosis and constructed a prognosis risk model with seven AGs, including APP, CDKN2A, EGFR, HSPD1, IL2RG, PLAU and VEGFA (Figure 1C) that revealed a robust performance signature for predicting prognosis compared to clinicopathological factors in training and multiple validation sets (Figure 3). This evidence concerns the gene PLAU and head and neck squamous cell carcinoma.