β-Actin (ACTB): From Housekeeping Gene to Clinical Biomarker – Insights into Diagnostic, Prognostic, and Predictive Applications

Abstract

Beta-actin (ACTB), a highly conserved cytoskeletal protein, plays essential roles in cell migration, adhesion, and transcriptional regulation. Traditionally used as a housekeeping gene for normalization in gene expression studies, emerging evidence reveals dysregulated ACTB expression and mutations in various diseases, including cancers and dystrophies, challenging its benign reference status. This review synthesizes the diagnostic, prognostic, and predictive values of ACTB across oncology and non-oncology contexts. ACTB expression alterations serve as early detection biomarkers detected via liquid biopsies in cancers, and as indicators of fibrosis or neurodegeneration. Prognostically, elevated ACTB correlates with aggressive phenotypes and poor survival in colorectal and other cancers, driven by mechanisms linked to epithelial-mesenchymal transition, metastasis, and immune evasion. Predictively, ACTB polymorphisms and expression levels influence chemotherapy response in ovarian cancer and immunotherapy effectiveness through modulation of T-cell migration. Translational progress from preclinical models, including CRISPR-based knockouts, to emerging clinical trials highlights potential clinical applications while underscoring gaps like assay standardization, ethnic variability, and prospective validation needs. Ethical and regulatory considerations stress equitable access and rigorous biomarker validation. Future directions involve AI-driven analytics, nanotechnology-enabled targeting, and multi-omics biomarker integration to harness ACTB’s full potential. Overall, ACTB represents a versatile yet underexploited biomarker promising to enhance precision diagnostics and therapeutics.