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

Hanping He; Feng Yuan; Ying Li; Guoliang Pi; Hongwei Shi; Yanping Li; Guang Han

doi:10.2174/0115734099302492240405065505

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

Curr Comput Aided Drug Des. 2024 Apr 16. doi: 10.2174/0115734099302492240405065505. Online ahead of print.

Authors

Hanping He¹, Feng Yuan¹, Ying Li¹, Guoliang Pi¹, Hongwei Shi¹, Yanping Li¹, Guang Han¹

Affiliation

¹ Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

PMID: 38629358
DOI: 10.2174/0115734099302492240405065505

Abstract

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.

Keywords: FOXD2; MSI; head and neck squamous cell carcinoma; immune infiltration; prognosis; therapeutic target.