Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer

Barrabés, Sílvia; Llop, Esther; Ferrer-Batallé, Montserrat; Ramírez, Manel; Aleixandre, Rosa Núria; Perry, Antoinette S.; Llorens, Rafael de; Peracaula, Rosa

doi:10.1016/j.cca.2017.05.009

Cited by 13 publications

(15 citation statements)

References 29 publications

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“…Several studies, mostly based on enzyme-linked lectin assays (ELLA), have been applied to assess whether differences in terminal or core-fucosylation of PSA in urine, seminal fluid, blood, or tissue enable discrimination of BPH from PCa or identification of aggressive PCa. 18,42,52,53 These lectin immunoassays have the same basic format as a standard enzymelinked immunosorbent assay (ELISA), in which one antibody is replaced by a lectin recognizing carbohydrate moieties. However, reports with contradictory results have been described which might be due to the Comparison of ROC curves for free PSA, total PSA, %-free PSA, and %-core-fucosylated PSA standardized to total PSA determined by ECLIA (%-fuc-PSA-ECLIA).…”

Section: Discussionmentioning

confidence: 99%

“…In former lectin-based studies, patient samples with higher serum concentrations (up to 110 ng/mL) or urine samples with very high total PSA levels by nature (mg/mL range) were analyzed. 6,42,53 This is largely because of the lack in sensitivity of these assays as lectins possess 100-10,000-fold lower binding affinities than antibodies. 54 In addition, low specificity of lectins toward glycan structures and their unspecific binding to glycoproteins from human matrix is an inherent problem of lectins resulting in high background signals obscuring the analyte signal of interest and worsening the limit of detection.…”

Section: Discussionmentioning

confidence: 99%

“…38,39 Changes in glycosylation of PSA associated with PCa development and progression have been analyzed in several foundational studies focusing on human samples of different origin including prostate tissue, cell lines, seminal fluid, urine, and serum. [40][41][42][43][44] These studies span the breadth from whole glycoform profiling to targeted analysis of single glycan modifications such as terminal sialylation or site-specific core-fucosylation. 6,45 With regard to the evaluation of glycosylation changes of PSA in human serum as prognostic and diagnostic marker for PCa, some of these assays lack in sensitivity for usage in the critical gray area ranging from 4 to 10 ng/mL total PSA or have not been tested using statistically significant sample numbers.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…The explanation is that the level of PSA from a tumour tissue cannot reach the urine, with only a minor level of aberrantly glycosylated PSA present in urine [52]. The low level of PSA with a-2,3-SA can also be explained by the preferential presence of the a-2,6-SA form on PSA in seminal plasma [68] and this form of PSA can be released into urine [52]. The AAL labelled with polystyrene nanoparticles doped with europium applied to the fluorescent ELISA format of the analysis has the potential for use in PSA glycoprofiling as a diagnostic PCa biomarker (PCa versus BPH) with p ¼ 0.03 [62].…”

Section: Analysis In Urine 421 Diagnostic Prostate Cancer Biomarkersmentioning

confidence: 99%

Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer

et al. 2019

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The initial part of this review details the controversy behind the use of a serological level of prostate-specific antigen (PSA) for the diagnostics of prostate cancer (PCa). Novel biomarkers are in demand for PCa diagnostics, outperforming traditional PSA tests. The review provides a detailed and comprehensive summary that PSA glycoprofiling can effectively solve this problem, thereby considerably reducing the number of unnecessary biopsies. In addition, PSA glycoprofiling can serve as a prognostic PCa biomarker to identify PCa patients with an aggressive form of PCa, avoiding unnecessary further treatments which are significantly life altering (incontinence or impotence).

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“…Another recent study investigated the glycosylation features of PSA in urinary samples collected after DRE by using an immunopurification step. 13 Lectins were used to investigate the level of core fucosylation and the presence of α2,6-linked sialic acids, revealing, however, no association with the pathology of the disease (Gleason score). This observation could result from the rather small sample size (18 controls vs 36 PCa cases) and the only partial cover of sialic acid linkages, because only the levels of α2,6-sialic acids were considered.…”

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confidence: 99%

An In-Depth Glycosylation Assay for Urinary Prostate-Specific Antigen

et al. 2018

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The concentration of prostate-specific antigen (PSA) in serum is used as an early detection method of prostate cancer (PCa); however, it shows low sensitivity, specificity, and a poor predictive value. Initial studies suggested the glycosylation of PSA to be a promising marker for a more specific yet noninvasive PCa diagnosis. Recent studies on the molecular features of PSA glycosylation (such as antenna modification and core fucosylation) were not successful in demonstrating its potential for an improved PCa diagnosis, probably due to the lack of analytical sensitivity and specificity of the applied assays. In this study, we established for the first time a high-performance PSA Glycomics Assay (PGA), allowing differentiation of α2,6- and α2,3-sialylated isomers, the latter one being suggested to be a hallmark of aggressive types of cancer. After affinity purification from urine and tryptic digestion, PSA samples were analyzed by CE-ESI-MS (capillary electrophoresis–electrospray ionization coupled to mass spectrometry). Based on positive controls, an average interday relative standard deviation of 14% for 41 N-glycopeptides was found. The assay was further verified by analyzing PSA captured from patients’ urine samples. A total of 67 N-glycopeptides were identified from the PSA pooled from the patients. In summary, the first PGA successfully established in this study allows an in-depth relative quantitation of PSA glycoforms from urine. The PGA is a promising tool for the determination of potential glycomic biomarkers for the differentiation between aggressive PCa, indolent PCa, and benign prostate hyperplasia in larger cohort studies.

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Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer

Cited by 13 publications

References 29 publications

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

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

Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer

An In-Depth Glycosylation Assay for Urinary Prostate-Specific Antigen

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