Comprehensive Analysis and Experimental Validation of FOXD2 as a Novel Potential Prognostic Biomarker Associated with Immune Infiltration in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: The role of Forkhead Box D2 (FOXD2) in head and neck squamous cell carcinoma (HNSC) has never been studied.

OBJECT: Our object was to explore the role of FOXD2 in HNSC.

METHODS: Clinical data for patients with HNSC was obtained from TCGA. Our study examined the atypical expression of FOXD2 in both HNSC and pan-cancer, along with its diagnostic and prognostic implications, as well as the association between FOXD2 expression and clinical characteristics, immune infiltration, immune checkpoint genes, and MSI. Gene set enrichment analysis (GESA) was used to investigate the potential regulation network of FOXD2 in HNSC. We analyze the genomic alterations of FOXD2 in HNSC. GSE13397 and qRT-PCR were used for the validation of FOXD2 expression.

RESULTS: FOXD2 was aberrantly expressed in 24 tumors. FOXD2 was significantly up-regulated in HNSC compared to normal head and neck tissue (p < 0.001). High FOXD2 expression was associated with the histologic grade of the patient with HNSC (p < 0.001), lymphovascular infiltration (p = 0.002) and lymph node neck dissection (p = 0.002). In HNSC, an autonomous correlation between FOXD2 expression and OS was observed (HR: 1.36; 95% CI: 1.04-1.78; p = 0.026). FOXD2 was associated with the neuronal system, neuroactive ligand-receptor interaction, and retinoblastoma gene in cancer. FOXD2 was associated with immune infiltration, immune checkpoints, and MSI. The somatic mutation rate of FOXD2 in HNSC was 0.2%. FOXD2 was significantly up-regulated in HNSC cell lines.

CONCLUSION: Our findings suggest that FOXD2 has the potential to serve as a prognostic biomarker and immunotherapeutic target for individuals with HNSC.