Gene amplification and protein overexpression of FLNA in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a common cancer with several risk factors. Filamin A (FLNA), an actin-binding protein, plays a role in cytoskeletal remodeling and tumor progression; however, its specific role in HNSCC is still unclear. In this study, we aimed to examine the amplification of the FLNA gene, along with its mRNA and protein overexpression, and evaluate their clinical significance in patients with HNSCC using multi-omics datasets and independent validation.

Genetic alterations in the FLNA gene were investigated using the cBioPortal, and the expression profiles were analyzed in UALCAN by integrating TCGA and CPTAC datasets. The expression of FLNA was validated in HNSCC and adjacent non-tumor tissue samples through real-time PCR; protein levels were determined from immunohistochemical data of the Human Protein Atlas. The Kaplan-Meier plotter was used for the prognostic analysis of HNSCC patients with FLNA expression. Furthermore, protein interaction networks were constructed using the Human Protein Atlas, followed by functional enrichment analysis via Metascape.

FLNA was altered in 7 % of HNSCC patients, primarily through FLNA amplification, which was linked to increased mRNA expression (p < 0.001). Moreover, FLNA mRNA and protein were significantly expressed in HNSCC tissues compared to non-tumor tissue samples (p < 0.001). High FLNA expression was associated with advanced clinical stages, high histological grades, lymph node metastasis, and shorter overall survival (p < 0.01). From the protein-protein interaction network, FLNA was central to pathways involved in focal adhesion, cell adhesion, and extracellular matrix interaction. These pathways are strongly associated with cancer development and progression.

These findings suggest that amplification and overexpression of FLNA could serve as a potential prognostic biomarker in HNSCC.