Comprehensive Biochemical Insights into Prostate-Specific Antigen: From Biomarker to Functional Mediator in Prostate Cancer Pathophysiology

Prostate-Specific Antigen (PSA) is a glycoprotein produced in the prostate and is widely used as a biomarker for the diagnosis of prostate cancer (PCa). Although elevated PSA levels are often associated with PCa, several noncancerous conditions can also lead to increased PSA. In addition to total PSA, various PSA isoforms are detectable in the blood of patients, and their levels may differ depending on the underlying pathophysiological condition, whether benign or malignant. Measuring serum PSA levels alone is not sufficient to detect PCa, leading to widespread overdiagnosis and overtreatment. Therefore, comprehensive biochemical insights into PSA and its isoforms, of normal, benign, and malignant origin, may improve PSA assays for PCa diagnosis. Apart from its role as a biomarker, PSA plays multiple roles in the pathophysiology of PCa by activating the Epithelial-Mesenchymal Transition (EMT) and promoting tumor progression, as well as regulating the invasion and metastasis of PCa cells. In PCa, elevated PSA levels are associated with immunosuppression, antiapoptotic properties, and inhibition of angiogenesis. A comprehensive review of numerous important research findings on PSA and its isoforms was conducted to elucidate the role of PSA as a biomarker and functional mediator in PCa pathophysiology. Thus, the use of PSA as a biomarker for the diagnosis of PCa can minimize unnecessary and inappropriate biopsies, identify suitable patients for prostate biopsy, ensure early diagnosis, and initiate treatment at an early stage of PCa. Furthermore, the role of PSA as a functional mediator will enable us to study the pathophysiology of patients with prostate cancer (PCa).