J Cancer 2021; 12(3):693-702. doi:10.7150/jca.47978

Research Paper

Diagnostic and prognostic value of FOXD1 expression in head and neck squamous cell carcinoma

Shijie Qiu1,2#, Dan Li3#, Zhisen Shen1,2, Qun Li1,2, Yi Shen1,2, Hongxia Deng1,2, Yidong Wu1,2, Chongchang Zhou1,2✉

1. Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China.
2. Department of Otorhinolaryngology Head and Neck Surgery, Lihuili Hospital affiliated to Ningbo University, Ningbo, Zhejiang, China.
3. Department of Cardiology, The Second Hospital of Yinzhou, Ningbo, Zhejiang, China.
#These authors contributed equally to this work.

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Qiu S, Li D, Shen Z, Li Q, Shen Y, Deng H, Wu Y, Zhou C. Diagnostic and prognostic value of FOXD1 expression in head and neck squamous cell carcinoma. J Cancer 2021; 12(3):693-702. doi:10.7150/jca.47978. Available from https://www.jcancer.org/v12p0693.htm

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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.

Keywords: FOXD1, bioinformatics, head and neck squamous cell carcinoma, prognosis, survival