THE ACTIVITY OF PROTEOLYTIC ENZYMES AND THEIR INHIBITORS IN THE SECRETION OF THE PROSTATE IN ITS BENIGN HYPERPLASIA AND CANCER

Background. Prostate-specific antigen is the most commonly used serum marker for the early detection of prostate cancer (PC). However, the specificity of the test is low and accounts for about 20%. The study of the regulatory functions of proteinases and their inhibitors in carcinogenesis is promising in terms of developing methods for the early cancer diagnosis.

Objective: to analyze impaired proteolytic processes in the secretion of the prostate in its benign hyperplasia (BPH) and PC, by determining the key indicators of the kallikrein-kinin and renin-angiotensin systems and the activity of leukocyte elastase in the prostatic secretion.

Subjects and methods. Group 1 included 20 patients with PC (mean age 62.7±2.3 years). Group 2 comprised 20 men with BPH (mean age 62.2±1.4 years). A control group consisted of 20 healthy men (mean age 35.6±4.5 years). The prostatic secretions from the patients of all the groups were used to estimate the indicators of proteolytic systems: kallikrein activity, prekallikrein levels, the inhibitory activity of α1-proteinase inhibitor (α1-PI), and α2-macroglobulin (α2-MG), and the activity of angiotensin-converting enzyme (ACE) and elastase and elastase-like activity.

Results. Comparative analysis of the specific features of impaired proteolytic processes during benign and malignant prostate processes indicated that in PC the prostatic secretion showed a 39.2% increase in the activity of kallikrein (p < 0.001) and a 41.3% reduction in that of ACE (p < 0.001) as compared to those in BPH, which seems to reflect a decrease in prostatic secretion angiotensin II levels. PC is characterized by a drastic rise in the inhibitory potential of prostatic secretion; for the prostatic secretion activities of α1-PI and α2-MG are 56.9 (p < 0.001) and 96.8% (p < 0.001) respectively, higher than those in BPH. There are 2 statistically significant criteria for PC diagnosis: the activity of kallikrein and ACE with 75.0% specificity and 66.7% sensitivity.

Conclusion. An imbalance between proteinases and their inhibitors has been found in the prostatic secretion in PC and BPH, which is the basis for biochemical individuality of cancer transformation processes in the prostate and may be used in future as a marker for the diagnosis of PC.

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