PSA reactivity in extracellular microvesicles to commercial immunoassays

Area of Science:

• Biochemistry
• Oncology
• Nanomedicine

Background:

• Prostate-specific antigen (PSA) is a key biomarker for prostate cancer (PCa).
• Circulating PSA exists in various forms, including those associated with extracellular vesicles (EVs).
• Understanding PSA within EVs is crucial for refining diagnostic approaches.

Purpose of the Study:

• To characterize prostate-specific antigen (PSA) within extracellular vesicles (EVs).
• To evaluate the reactivity of EV-bound PSA with commercial immunoassay methods.
• To explore the diagnostic potential of measuring EV-bound PSA.

Main Methods:

• Analysis of EVs isolated from serum of prostate cancer (PCa), benign prostatic hyperplasia (BPH) patients, and healthy controls.
• Quantification of total (ev-T-PSA) and free (ev-F-PSA) using commercial immunoassays.
• Direct measurement of PSA in specific EV populations (CD81+, CD63+) via immunocapture-ELISA (IC-ELISA).

Main Results:

• EV-bound T-PSA (ev-T-PSA) was detected in all analyzed samples.
• The ratio of ev-T-PSA to serum T-PSA was higher in samples with lower serum T-PSA levels (< 4 µg/L).
• EV-T-PSA levels were lower in PCa patients compared to healthy controls and BPH patients, with significant differences observed between commercial assays.

Conclusions:

• Extracellular vesicle-bound PSA represents a distinct form of circulating PSA.
• Measurement of EV-bound PSA is feasible using automated immunoassays in clinical settings.
• This finding may enhance the utility of PSA as a biomarker in prostate cancer diagnostics.