BERKELEY, CA (UroToday.com) - The reliability and accuracy of the prostate-specific antigen (PSA) blood test for prostate tumor diagnosis and follow up has recently come under scrutiny. This is an issue of utmost clinical significance since PSA testing, combined with digital rectal examination, is commonly used for early identification of prostate tumors. If the PSA test produces false positive/negative results it will lead to unnecessary biopsy, anxiety as well as discomfort for the patient or put him in danger for developing undiagnosed disease that may lead to the death of a patient. Despite a large number of available biomarkers in prostate cancer, only the PSA blood test is commonly used.
PSA is an enzyme produced by cells of the prostate gland, and its expression is dependent on activation and signaling of the androgen receptor. One of the potential physiological functions attributed to PSA is the dissolution of the coagulum. However, a complete understanding of the role of PSA in the prostate gland is not yet clear. PSA is a kallikrein-related peptidase secreted by the epithelial cells of the prostate gland and are able to digest some proteins in a very specific manner. We checked its ability to digest the galectin-3 as its expression is associated with prostate cancer invasion and metastasis.
Galectin-3 is a member of the galectin gene family and contains a carbohydrate-recognition-binding domain of about 130 amino acids that enable the specific binding of β-galactosides and is abundantly expressed in prostate and other cancer inflamed tissues. Galectin-3 is a target of PSA in semen and can be cleaved after the amino acid tyrosine at position 107. This tyrosine is phosphorylated by c-Abl tyrosine kinase . Since galectin-3 phosphorylated at tyrosine 107 is resistant to cleavage by PSA, and associated with increased multivalency as well as increased angiogenesis in prostate, we questioned if an increased level of galectin-3 in the blood is associated with prostate cancer status and might serve as a complementary marker to PSA to increase its validity and the decrease false positive and negative results associated with PSA blood test. We also suggested that cleavage status of galectin-3 in the prostate tissue might be associated with tumor formation and progression of prostate cancer. The results demonstrate that the differences in galectin-3 levels in the serum showed an association with disease status. We would like to stress that this is the first study showing that patients with metastatic prostate cancer have higher serum levels of galectin-3 as compared with non-cancer control patients. However, we should also stress that this study has tested a small sample size (8 patients in each patient group), as well as the fact that only the most extreme category (metastatic disease) of prostate cancer was included as the cancer group.
In the near future we will conduct a larger clinical study to validate our initial findings, which should include newly diagnosed clinically localized prostate cancer, or patients with no evidence of disease recurrence after local therapy, or patients with rising PSA after local therapy. We expect that galectin-3 may be a useful serum marker, complementary to the PSA blood test, and could be used in patients with low or high level of PSA to confirm disease status, therapeutic response, and/or recurrence prostate cancer.
Written by:
Vitaly Balan, Yi Wang and Avraham Raz as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit
Galectin-3: A possible complementary marker to the PSA blood test - Abstract
More Information about Beyond the Abstract