FAM3D regulation of head and neck squamous cell carcinoma behaviour through the EMT pathway

Abstract Objectives Head and neck squamous cell carcinoma present challenges in effective treatment, with 50%–60% of cases exhibiting recurrence or metastasis, often resistant to surgery alone. Immunotherapy, a promising approach, does not guarantee benefits for all patients. Thus, the imperative lies in identifying reliable biomarkers for predicting immunotherapy efficacy. FAM3D, a protein‐coding gene known for its potent chemotactic activity in human peripheral blood monocytes and neutrophils, plays a crucial role in regulating tumour immune responses and holds promise as an immune biomarker. Materials and Methods We employed comprehensive database analysis to scrutinise FAM3D, evaluating its gene expression, mutation profiles and prognostic implications in head and neck squamous cell carcinoma, along with its associations with clinical characteristics and immune cell infiltration. Complementary functional experiments were conducted to delve into the potential mechanisms governed by FAM3D. Results Our findings establish a significant correlation between low FAM3D expression and the invasiveness and metastatic potential of head and neck squamous cell carcinoma. FAM3D likely exerts its influence through the regulation of epithelial–mesenchymal transition. Conclusions FAM3D emerges as a valuable biomarker for predicting the responsiveness of patients with head and neck squamous cell carcinoma to immunotherapy, holding substantial clinical diagnostic and therapeutic relevance.