Abstract
SummaryBackgroundProstate-specific antigen (PSA) is a glycoprotein tumor marker known to exist as numerous glycospecies. Investigations on its glycobiochemical properties aimed at their use in the preparation of adjuncts in determining PSA concentration for clinical purposes have accumulated a lot of data on its structural properties. In this study, we reconsidered unexplored ubiquitously present low molecular mass species of PSA regarding to molecular mass, origin and pathophysiological source specificity in order to evaluate them as biomarkers.MethodsData on low molecular mass PSA-immunoreactive species from sera of subjects with prostate cancer (PCa), benign prostatic hyperplasia (BPH), breast cancer (BCa), and urine of healthy males obtained by on-chip immunoaffinity chromatography combined with mass spectrometry were analyzed.ResultsThe results obtained indicated PSA species common to BCa, PCa, and BPH at 12-13 kDa, 17-19 kDa and 21-24 kDa. The striking difference in predominant frequencies made the profile characteristic in each examined pathophysiological condition. On the other hand, paired groups of prostatic and extraprostatic PSA contained rare species with small differences among groups concerning individual species. Low molecular mass PSA also included rare species unique for each group of samples.ConclusionThe results obtained revealed that uniformity of low molecular mass PSA-immunoreactive species in sera prevails over diversity related to cancer and non-cancer conditions, but at the same time some of them are molecules with biomarker potential for BPH detection.
Highlights
As a heterogeneous disease, blood-based diagnostics of prostate cancer (PCa) is very demanding and, in spite of many efforts, finding suitable biomarkers is still a challenging task [1, 2]
Data on low molecular mass prostate-specific antigen (PSA)-immunoreactive species from sera of subjects with prostate cancer (PCa), benign prostatic hyperplasia (BPH), breast cancer (BCa), and urine of healthy males obtained by on-chip immunoaffinity chromatography combined with mass spectrometry were analyzed
In the 1980s introduction of prostate-specific antigen (PSA), an enzyme produced by prostate epithelial cells, as an organ-specific marker had a favorable impact on monitoring the progression or recurrence of PCa [3]
Summary
Blood-based diagnostics of prostate cancer (PCa) is very demanding and, in spite of many efforts, finding suitable biomarkers is still a challenging task [1, 2]. PSA is known to exist as numerous molecular species differing in activity and molecular mass, depending on both peptide and oligosaccharide moieties and these changes under pathophysiological conditions [6,7,8,9]. They result from diverse routes of PSA processing, alternative splicing and glycosylation, reflecting normal prostate biology [10, 11]. Proteomic and glycomic approaches that open new possibilities in the field of biomarkers in general, provide an opportunity to take advantage of the structural heterogeneity of the PSA molecule in the search for better diagnostic tools for PCa [13, 18,19,20]. The lack of an ideal tumor marker and the necessity to combine different markers rather than using a single one, provide room for applying PSA molecular species in their full context
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