In-Depth Glycoproteomic Assay of Urinary Prostatic Acid Phosphatase

IF 4.6 Q1 CHEMISTRY, ANALYTICAL ACS Measurement Science Au Pub Date : 2023-12-07 DOI:10.1021/acsmeasuresciau.3c00055
Wei Wang, Carmen R. de Nier, Manfred Wuhrer and Guinevere S.M. Lageveen-Kammeijer*, 
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Abstract

Prostate-specific antigen (PSA) is a well-known clinical biomarker in prostate cancer (PCa) diagnosis, but a better test is still needed, as the serum-level-based PSA quantification exhibits limited specificity and comes with poor predictive value. Prior to PSA, prostatic acid phosphatase (PAP) was used, but it was replaced by PSA because PSA improved the early detection of PCa. Upon revisiting PAP and its glycosylation specifically, it appears to be a promising new biomarker candidate. Namely, previous studies have indicated that PAP glycoforms differ between PCa and non-PCa individuals. However, an in-depth characterization of PAP glycosylation is still lacking. In this study, we established an in-depth glycoproteomic assay for urinary PAP by characterizing both the micro- and macroheterogeneity of the PAP glycoprofile. For this purpose, PAP samples were analyzed by capillary electrophoresis coupled to mass spectrometry after affinity purification from urine and proteolytic digestion. The developed urinary PAP assay was applied on a pooled DRE (digital rectal examination) urine sample from nine individuals. Three glycosylation sites were characterized, namely N94, N220, and N333, via N-glycopeptide analysis. Taking sialic acid linkage isomers into account, a total of 63, 27, and 4 N-glycan structures were identified, respectively. The presented PAP glycoproteomic assay will enable the determination of potential glycomic biomarkers for the early detection and prognosis of PCa in cohort studies.

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尿液前列腺酸性磷酸酶的深度糖蛋白组测定
前列腺特异性抗原(PSA)是诊断前列腺癌(PCa)的著名临床生物标志物,但由于基于血清水平的 PSA 定量特异性有限且预测价值不高,因此仍需要更好的检测方法。在 PSA 之前,人们使用前列腺酸性磷酸酶(PAP),但由于 PSA 提高了 PCa 的早期检测率,PAP 被 PSA 所取代。重新审视前列腺酸性磷酸酶及其糖基化特性后,它似乎是一个很有希望的候选生物标记物。也就是说,以前的研究表明 PCa 患者和非 PCa 患者的 PAP 糖基化形式不同。然而,目前仍缺乏对 PAP 糖基化的深入研究。在本研究中,我们通过表征 PAP 糖型的微观和宏观异质性,建立了尿液 PAP 的深入糖蛋白组学检测方法。为此,在对尿液进行亲和纯化和蛋白水解消化后,采用毛细管电泳结合质谱法对 PAP 样品进行了分析。所开发的尿液 PAP 检测方法适用于来自九个人的 DRE(数字直肠检查)尿液样本。通过 N-糖肽分析,确定了三个糖基化位点,即 N94、N220 和 N333。考虑到半乳淀粉酸连接异构体,共鉴定出 63、27 和 4 个 N-糖结构。所介绍的 PAP 糖蛋白组测定方法将有助于确定潜在的糖生物标记物,以便在队列研究中对 PCa 进行早期检测和预后判断。
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ACS Measurement Science Au
ACS Measurement Science Au 化学计量学-
CiteScore
5.20
自引率
0.00%
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0
期刊介绍: ACS Measurement Science Au is an open access journal that publishes experimental computational or theoretical research in all areas of chemical measurement science. Short letters comprehensive articles reviews and perspectives are welcome on topics that report on any phase of analytical operations including sampling measurement and data analysis. This includes:Chemical Reactions and SelectivityChemometrics and Data ProcessingElectrochemistryElemental and Molecular CharacterizationImagingInstrumentationMass SpectrometryMicroscale and Nanoscale systemsOmics (Genomics Proteomics Metabonomics Metabolomics and Bioinformatics)Sensors and Sensing (Biosensors Chemical Sensors Gas Sensors Intracellular Sensors Single-Molecule Sensors Cell Chips Arrays Microfluidic Devices)SeparationsSpectroscopySurface analysisPapers dealing with established methods need to offer a significantly improved original application of the method.
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