Stratification of HNSCC patients in the TCGA cohort and validation in four independent cohorts, according to the 23 FAT1‐associated signature genes. (A) The TCGA HNSCC patients were classified into FAT1‐LR (n = 195) and FAT1‐HR (n = 371) subgroups by performing hierarchical clustering. The mRNA expression level in each FAT1‐associated signature gene was converted into a z‐score and shown in a heatmap with row normalized values. (B, C) Five‐year OS and RFS rates of each group were determined using Kaplan–Meier plots. The FAT1‐HR subgroup showed significantly lower five‐year OS and RFS rates than the FAT1‐LR subgroup (P = 0.01 and 0.003, respectively). (D‐F) Predicted outcomes in the four independent HNSCC cohorts using FAT1 signature were also depicted using Kaplan–Meier plots. Five‐year OS rates of each group were determined in the Leipzig (n = 270), FHCRC (n = 97), and MDACC cohorts (n = 74; P = 0.02, 0.02, and 0.01, respectively). (G) Also, five‐year RFS rates of each group were determined in the KHUMC cohort (n = 72, P = 0.1). Log‐rank test was used to estimate the P value. *P < 0.05. HNSCC, head and neck squamous cell carcinoma; FAT1‐HR, FAT1‐associated high risk; FAT1‐LR, FAT1‐associated low risk; OS, overall survival; RFS, recurrence‐free survival.