Clinical Implications of ACTN4 in Oral Cancer: Biomarker for Prognosis and Therapeutic Targeting

Abstract Alpha-actinin-4 (ACTN4) has emerged as a pivotal molecular biomarker in oral cancer, a malignancy with significant global burden and limited effective prognostic markers. Oral cancer prognosis remains challenging due to heterogeneous tumour behaviour and late diagnosis, underscoring the urgent need for reliable biomarkers and novel therapeutic targets. ACTN4, a cytoskeletal actin-binding protein, facilitates cancer progression by promoting cellular motility, invasion, and metastasis. Numerous studies reveal that ACTN4 overexpression correlates with aggressive tumour phenotype, poor patient prognosis, and resistance to conventional therapies in oral squamous cell carcinoma. Diagnostic evaluation of ACTN4 expression offers potential for early detection and risk stratification. Therapeutically, targeting ACTN4-mediated pathways could inhibit tumour invasiveness and improve treatment outcomes. This review synthesises current evidence supporting ACTN4’s dual role as a prognostic biomarker and therapeutic target in oral cancer, highlighting its translational potential for precision oncology and personalised treatment strategies to improve patient survival and quality of life. Keywords: ACTN4, oral cancer, tumour, metastasis