Comprehensive biochemical insights into derivatives of PSA and glycosylation-specific changes in PSA: role in diagnosis and management of prostate cancer

BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed cancer in men worldwide, and prostate-specific antigen (PSA) test is currently the standard of choice for PCa diagnosis. Globally, several methods are employed for diagnosis of PCa, and each holds a unique role and importance. Serum PSA test and Magnetic Resonance Imaging (MRI) are widely used for diagnosis of PCa; however, MRI has certain limitations and disadvantages compared to PSA test. Moreover, growing evidences suggest that solely simple testing of serum PSA levels to diagnose PCa leads to widespread overdiagnosis and overtreatment. This is because simple PSA test has certain limitations, including lack of specificity, elevation in Benign Prostatic Hyperplasia (BPH) and inability to detect a significant number of PSA-negative tumors. Additionally, serum PSA levels do not directly correlate with higher grades and stages of PCa. MAIN BODY: The purpose of this manuscript is to provide comprehensive and up-to-date knowledge, critical perspectives, and practical applications of derivatives of PSA and glycosylation-specific changes in PSA, with the aim of minimizing unnecessary and excessive biopsy in patients suspected of having PCa. Therefore, the use of various derivatives of PSA was focused here to increase the sensitivity and specificity of serum PSA for diagnosis of PCa. In addition to PSA levels, glycan structure of PSA changes with progression of PCa, which suggest that aberrant PSA glycosylation increases as PCa progresses. Differences in the glycan structure of PSA enable to distinguish normal PSA from cancerous origin, suggesting an important biochemical application of glycan structure of PSA in the diagnosis of PCa. Thus, present study highlights the role of derivatives of PSA and glycosylation-specific changes in PSA in the diagnosis and management of PCa. Additionally, this article emphasizes integration of glycan-based assays with PSA derivatives into multi-analyte panels, paving the way for more sensitive and specific diagnosis of PCa and aiding in the management of PCa. CONCLUSION: The manuscript will provide extensive information to minimize superfluous biopsies, identify patients truly needing biopsy, differentiate BPH from PCa, distinguish indolent from aggressive PCa, enable early diagnosis and treatment at early-stage, monitor treatment response and early detection of recurrence.