PLS3 Is a Prognostic Biomarker and Correlates with Immune Infiltrates in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) features aggressive progression and a complex immunosuppressive microenvironment, contributing to poor patient prognosis and highlighting the need to identify key molecular drivers. The actin‑binding protein PLS3 (Plastin‑3) is involved in tumor metastasis, yet its expression, function, and therapeutic potential in HNSCC remain unclear. METHODS: PLS3 expression was analyzed via polymerase chain reaction (PCR), Western blot (WB), and immunohistochemistry (IHC). PLS3 was knocked down in vitro to assess its effects on HNSCC cell functions, and in vivo models were established to evaluate tumor progression and immune microenvironment. Bioinformatics analyses explored the relationship between PLS3 and tumor immunity. RESULTS: PLS3 was upregulated in HNSCC tissues and correlated with adverse clinical outcomes. Knockdown of PLS3 inhibited cell proliferation, migration, and invasion in vitro, and suppressed tumor growth in vivo. Mechanistically, PLS3 promoted HNSCC progression by activating the epithelial-mesenchymal transition (EMT) program. Bioinformatics and animal studies further linked PLS3 overexpression to an immunosuppressive microenvironment characterized by reduced CD8+ T-cell infiltration and downregulated chemokine expression. CONCLUSIONS: This study elucidates the oncogenic role of PLS3 in HNSCC and supports its potential as a prognostic biomarker and therapeutic target.