Inflammatory and Epigenetic Biomarkers in Prostate Disease: Current Evidence, Clinical Limitations, and Future Multimarker Strategies

Prostate disease diagnostics increasingly integrate PSA-derived parameters, molecular assays, risk calculators, and multiparametric MRI, yet important limitations remain in distinguishing benign inflammatory changes from clinically significant prostate cancer and in capturing biological heterogeneity. This narrative review summarizes current evidence on inflammatory and epigenetic biomarkers in prostate disease, focusing on YKL-40, mannose-binding lectin, and global DNA methylation/hydroxymethylation. The reviewed evidence indicates that chronic inflammation, innate immune variability, tumor microenvironment remodeling, and epigenetic dysregulation contribute to prostate disease progression and may provide biological information not fully reflected by conventional diagnostic tools. YKL-40 may reflect inflammatory stromal remodeling and angiogenic activity, mannose-binding lectin may represent innate immune variability, while DNA methylation and hydroxymethylation may indicate systemic molecular adaptation and long-term inflammatory imprinting. However, these biomarkers remain largely investigational and should currently be considered adjunctive biological layers rather than validated standalone diagnostic tools. Future studies should prioritize analytical standardization, prospective prostate-specific validation, and assessment of incremental clinical utility beyond PSA, molecular assays, and mpMRI within clearly defined contexts of use.