Abstract
FOXD1 has been reported to function as an oncogene in several types of cancer. This study evaluated the expression of FOXD1 and its role in head and neck squamous cell carcinoma (HNSCC). We mined the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases for expression profiles, clinical significance, and potential mechanisms of FOXD1in HNSCC. Our validation cohort consisted of FOXD1 mRNA expression in 162 paired HNSCC and adjacent normal tissues, as determined using quantitative real-time polymerase chain reaction. FOXD1 expression was upregulated in HNSCC in the public databases and in the validation cohort. The expression level of FOXD1 was associated with DNA amplification and methylation level. The areas under the curves (AUC) of TCGA cohort and the validation cohort were 0.855 and 0.843, respectively. Furthermore, higher FOXD1 expression was significantly associated with worse overall survival (hazard ratio [HR]: 1.849, 95% confidence interval [CI]: 1.280-2.670, P = 0.001) and a lower rate of recurrence-free survival (HR: 1.650, 95% CI: 1.058-2.575, P = 0.027) in patients with HNSCC. Moreover, gene set enrichment analysis showed that cases of HNSCC with FOXD1 overexpression were enriched in bladder cancer, cell cycle, DNA replication, glycosaminoglycan biosynthesis chondroitin sulfate, homologous recombination, glycan biosynthesis, nucleotide excision repair, p53 signaling pathway, pyrimidine metabolism, and spliceosome pathways. In summary, FOXD1 was significantly upregulated in HNSCC and was a good diagnostic biomarker and an independent predictor of poor survival and low rate of recurrence-free survival in patients with HNSCC.