Abstract

The prostate-specific antigen (PSA), a glycoprotein, is a clinically used biomarker for screen and diagnosis of prostate cancer. Most of PSA in blood circulation is protein-bound, and only a small fraction is present as free PSA. In general, the serum total PSA levels are <4ng/mL in healthy controls and significantly increased in certain prostate cancer patients. Currently, <0.25 in the ratio of free PSA to total PSA (F/T value) is used as an indicator of prostate cancer. The mRNA of PSA is mainly expressed in prostate, and its protein product is a protease present in seminal plasma for the liquefaction of seminal coagulum in normal physiology. The F/T value as a prostate cancer biomarker has been questioned for its benefit over harm caused by its high false-positive rate of diagnosis. Furthermore, the molecular basis of how PSA is getting into blood circulation from seminal plasma is largely unknown. In current study, a total of 24,692 clinical lab test results of serum F/T values from healthy controls and patients with 34 different types of diseases including different types of cancers and nonneoplasm illnesses during the past 5 years were collected and analyzed statistically. Our data showed that even though the prostate cancer patients had the lowest median serum F/T values, both significantly increased and decreased serum F/T values were associated with different types of human diseases, such as acute cerebral infarction, coronary heart disease, uremia, and nephrotic syndrome. The possible molecular mechanisms of serum PSA as disease biomarkers are discussed.

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