Circulating integrins as biomarkers for bone metastasis in prostate cancer

Bone complications are characteristic clinical complications of prostate cancer and a significant predictor of disease progression, morbidity, and patient care. Despite advancements in imaging and systemic therapies, current laboratory-based diagnostic methods, which predominantly focus on prostate-specific antigen (PSA), conventional radiology, and bone turnover markers, remain inadequate for the early correction of laboratory-based risk, identification of micrometastatic disease, and continuous monitoring of biochemical evidence of skeletal involvement in patients with metastatic castration-resistant prostate cancer (mCRPC). This diagnostic gap has heightened interest in circulating biomarkers that are analytically accessible and capable of recapitulating the biological mechanisms underlying bone-tropic metastatic progression. Mechanistic and clinical investigations have demonstrated that specific integrin subtypes generate a molecular signature associated with skeletal colonization by metastatic cells. This signature encompasses processes such as vascular arrest, transendothelial migration, adhesion to bone matrix components, and interactions with osteoblastic, immune, and stromal niches, all of which are reproducible and quantifiable. Integrins also appear in clinically relevant biofluids and cellular compartments, such as circulating tumor cells, extracellular vesicles, and bone marrow-resident disseminated tumor cells. This review synthesizes human clinical, translational, and population-based data linking circulating integrin-related signals with metastatic risk, disease progression, and outcomes associated with tumors and the skeletal system in patients with prostate cancer. We conducted a critical review of laboratory findings derived from liquid biopsies, including integrin-positive circulating tumor cells, extracellular vesicle-bound integrins, circulating extracellular matrix components, and integrin-regulated transcriptional and microRNA signatures. These findings were rigorously analyzed in terms of their diagnostic and prognostic efficacy compared to established clinical biomarkers. Registry-based and real-world evidence also highlights the clinical and laboratory implications of a failure to detect skeletal degeneration in a timely manner, which facilitates the consideration of integrin-related circulating markers as an add-on to diagnostic laboratory medicine processes.