Investigation on core-fucosylated prostate-specific antigen as a refined biomarker for differentiation of benign prostate hyperplasia and prostate cancer of different aggressiveness

Abstract

Prostate cancer represents a major cause of cancer death in men worldwide. Novel non-invasive methods are still required for differentiation of non-aggressive from aggressive tumors. Recently, changes in prostate-specific antigen glycosylation pattern, such as core-fucosylation, have been described in prostate cancer. The objective of this study was to evaluate whether the core-fucosylation determinant of serum prostate-specific antigen may serve as refined marker for differentiation between benign prostate hyperplasia and prostate cancer or identification of aggressive prostate cancer. A previously developed liquid chromatography-mass spectrometry/mass spectrometry-based strategy was used for multiplex analysis of core-fucosylated prostate-specific antigen (fuc-PSA) and total prostate-specific antigen levels in sera from 50 benign prostate hyperplasia and 100 prostate cancer patients of different aggressiveness (Gleason scores, 5-10) covering the critical gray area (2-10 ng/mL). For identification of aggressive prostate cancer, the ratio of fuc-PSA to total prostate-specific antigen (%-fuc-PSA) yielded a 5%-8% increase in the area under the curve (0.60) compared to the currently used total prostate-specific antigen (area under the curve = 0.52) and %-free prostate-specific antigen (area under the curve = 0.55) tests. However, our data showed that aggressive prostate cancer (Gleason score. 6) and nonaggressive prostate cancer (Gleason score ł 6) could not significantly (p-value = 0.08) be differentiated by usage of %fuc-PSA. In addition, both non-standardized fuc-PSA and standardized %-fuc-PSA had no diagnostic value for differentiation of benign prostate hyperplasia from prostate cancer. The %-fuc-PSA serum levels could not improve the differentiation of non-aggressive and aggressive prostate cancer compared to conventional diagnostic prostate cancer markers. Still, it is unclear whether these limitations come from the biomarker, the used patient cohort, or the imprecision of the applied method itself. Therefore, %-fuc-PSA should be further investigated, especially by more precise methods whether it could be clinically used in prostate cancer diagnosis.

Serum core‐type fucosylated prostate‐specific antigen index for the detection of high‐risk prostate cancer

“…32 However, the ratio of Fuc-PSA to total PSA could not improve the differentiation of nonaggressive and aggressive prostate cancer compared to PSA levels. 33 As mentioned above, several approaches have been used to measure glycosylated PSA. Mass spectrometry analysis or liquid chromatography analysis provide detailed information of glycosylation of PSA; however, the procedure is complex and prolonged measuring times make this technique infeasible for measuring specific glycosylated-PSA of many samples in the clinical setting.…”

“…Lang et al developed the sensitive assay to measure serum core‐type fucosylated PSA by an endoglycosidase‐assisted LC‐MS/MS‐based analysis 32 . However, the ratio of Fuc‐PSA to total PSA could not improve the differentiation of nonaggressive and aggressive prostate cancer compared to PSA levels 33 . Kekki et al reported a significant increase in PSA fucosylation in PCa tissue compared to benign tissue and in urine from PCa patients compared to BPH patients using a nanoparticle‐based AAL‐immunoassay for analyzing the fucosylation of PSA 34 .…”

Mass Spectrometry-Based Glycoproteomics and Prostate Cancer

“…Moreover, PSA testing lacks sufficient sensitivity, because serum levels of PSA do not necessarily increase in presence of advanced PCa. Another issue with PSA blood test is “the diagnostic grey zone” (men with blood concentrations of PSA between 4–10 ng/mL) in which only the 25% of patients have PCa, leading to the execution of many unnecessary biopsies [ 60 , 61 ]. Importantly, this test does not differentiate between indolent and aggressive forms of PCa.…”

Narrative review of urinary glycan biomarkers in prostate cancer

“…Many studies suggested the role of glycans as potential biomarkers for diseases (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54). A broad range of glycan alterations have been observed in blood-based or tissuebased analysis, including aberrant PSA glycosylation, increased sialylation, core fucosylation, O-GlcNAcylation, and branched N-glycan formation (55)(56)(57)(58)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71). Of fluid-based biomarkers, urine is one of the most minimally invasive and promising sources for the discovery of new biomarkers of PC and contains cells, DNA, RNA, proteins, extracellular vesicles (exosomes), and glycans (72)(73)(74)(75)(76)(77)(78)(79)(80).…”