Clinical significance of FAT1 gene mutation and mRNA expression in patients with head and neck squamous cell carcinoma

The FAT1 gene functions as a tumor suppressor or promoter and remains incompletely understood. We examined the clinical significance of FAT1 in head and neck squamous cell carcinoma (HNSCC) using four publicly available HNSCC cohorts and one HNSCC cohort enrolled at a tertiary medical center. We developed FAT1 signatures reflecting FAT1 mutations and mRNA expression using one cohort. Patients with HNSCC were classified into FAT1‐associated low risk (FAT1‐LR; n = 195) and FAT1‐associated high risk (FAT1‐HR; n = 371) subgroups. The five‐year overall survival and recurrence‐free survival rates were significantly lower in the FAT1‐HR subgroup than in the FAT1‐LR subgroup (P = 0.01 and 0.003, respectively). The clinical significance of FAT1 was validated using four independent cohorts. Cox proportional hazards models showed that the FAT1 signature was an independent prognostic factor for HNSCC patients. In addition, FAT1 signature was associated with the response to radiotherapy, advanced stage, and human papilloma virus (HPV) status in HNSCC patients. In conclusion, the FAT1 gene signature was associated with prognosis of HNSCC and may help to provide personalized treatments for HNSCC patients. In our study, we classified patients with head and neck squamous cell carcinoma (HNSCC) as FAT1‐associated low risk and FAT1‐associated high risk, based on our predefined FAT1 gene‐related molecular signature. The prognosis of patients with HNSCC was significantly different between both subgroups. In conclusion, the FAT1 signature served as an independent prognostic factor for HNSCC and was associated with response to radiation therapy.