Genomic and Transcriptomic Alterations in the COL28A1 Gene: Potential Role in the Pathogenesis of Head and Neck Squamous Cell Carcinoma

Objectives: Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent malignancies globally, often associated with tobacco, alcohol use, and human papillomavirus (HPV) infection. Recent studies have highlighted the importance of genetic alterations in the development and progression of HNSCC. The COL28A1 gene, a member of the collagen family, has not been extensively studied in the context of HNSCC pathogenesis. This study aimed to investigate the genomic and transcriptomic alterations of the COL28A1 gene in HNSCC and assess its potential role in disease progression, prognosis, and interaction with molecular pathways. Methods: Publicly available datasets from The Cancer Genome Atlas (TCGA) and Firehose Legacy were analyzed using bioinformatics platforms including cBioPortal, UALCAN, PolyPhen-2, I-Mutant, and STRING. Genomic alterations such as mutations, amplifications, and deletions were assessed, along with differential gene expression between tumor and normal tissues. Survival analysis was performed using Kaplan-Meier curves, and protein-protein interaction networks were constructed to explore functional associations. Results: COL28A1 alterations were identified in a subset of HNSCC and LUSC cases, primarily in the form of amplifications and missense mutations. Expression analysis revealed significantly elevated COL28A1 expression in HNSCC tumor tissues compared to adjacent normal tissues (p < 0.05). Survival analysis indicated that patients with higher COL28A1 expression had poorer overall survival. Pathogenicity predictions classified several mutations as "probably damaging," while protein stability analysis indicated reduced stability due to specific variants. Protein interaction analysis highlighted potential associations with extracellular matrix remodeling and cellular adhesion pathways. Conclusion: Genomic and transcriptomic alterations in COL28A1 may contribute to the pathogenesis and progression of HNSCC. Its elevated expression is associated with poorer prognosis, suggesting a potential role as a prognostic biomarker. Further functional studies are warranted to validate these findings and explore COL28A1 as a therapeutic target in HNSCC.