4.7 Article

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

Journal

MOLECULAR ONCOLOGY
Volume 16, Issue 8, Pages 1661-1679

Publisher

WILEY
DOI: 10.1002/1878-0261.13171

Keywords

FAT1; gene signature; head and neck squamous cell carcinoma; overall survival; recurrence-free survival

Categories

Funding

  1. National Research Foundation of Korea (NRF) - Korea government (MSIT) [2020R1A5A2019413]
  2. Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI20C1205]

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The FAT1 gene has both tumor suppressor and promoter functions in head and neck squamous cell carcinoma (HNSCC). Research has shown that the FAT1 gene signature is associated with prognosis, response to radiotherapy, advanced stage, and human papilloma virus (HPV) status in HNSCC patients.
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.

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