A sensitive assay to measure biomarker glycosylation demonstrates increased fucosylation of prostate specific antigen (PSA) in patients with prostate cancer compared with benign prostatic hyperplasia.
BACKGROUND
Prostate specific antigen (PSA) measurement is used for the diagnosis of prostate cancer (PCa) but the test lacks specificity due to the number of false positive readings. The glycosylation of PSA is altered in PCa but studies in this area have been limited to few clinical samples and/or require advanced laboratory facilities. An assay to assess PSA glycosylation was established using equipment available in most routine biomedical testing laboratories.


METHODS
Serum samples from patients with PCa or benign prostatic hyperplasia (BPH) were used. PSA (range 4-10 ng/ml) was affinity purified, separated and probed with the lectin Ulex europaeus (UEA-1; specific for α1,2 linked fucose). An enzyme-linked immunosorbent lectin assay (ELLA) with colorimetric detection was devised and PSA fucosylation assessed in a further independent set of 26 samples.


RESULTS
Free PSA (fPSA) from PCa patients showed a significant increase in fucosylation compared with fPSA from patients with BPH. The ELLA was 92% specific and 69% sensitive for PCa over BPH. In comparison, fPSA measurement was 70% specific and 56% sensitive (threshold set to 25% tPSA) for PCa over BPH.


CONCLUSIONS
Changes in glycosylation of PSA were identified using 50 μl of serum with PSA in the range of 4-10 ng/ml, this represents a more specific and sensitive test for PCa based on fucosylation changes of fPSA.
Dwek
Miriam V
MV
Department of Molecular and Applied Biosciences, University of Westminster, London, UK. m.v.dwek@westminster.ac.uk
Jenks
Andrew
A
Leathem
Anthony J C
AJ
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001774:Blood Chemical Analysis / Q000379:methods*; D005643:Fucose / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008297:Male; D008875:Middle Aged; D037121:Plant Lectins / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000097:blood / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism*
D015415:Biomarkers; D037121:Plant Lectins; C036850:Ulex europaeus lectins; D005643:Fucose; D017430:Prostate-Specific Antigen