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检测含有 N,N-二乙酰乳糖胺(LacdiNAc)的游离前列腺特异性抗原,用于早期前列腺癌诊断和识别去势抵抗性前列腺癌患者。

Detection of N,N-diacetyllactosamine (LacdiNAc) containing free prostate-specific antigen for early stage prostate cancer diagnostics and for identification of castration-resistant prostate cancer patients.

机构信息

Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava 845 38, Slovakia; Glycanostics, Ltd., Dubravska cesta 9, Bratislava 845 38, Slovakia.

Institute of Chemistry, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava 845 38, Slovakia.

出版信息

Bioorg Med Chem. 2021 Jun 1;39:116156. doi: 10.1016/j.bmc.2021.116156. Epub 2021 Apr 20.

DOI:10.1016/j.bmc.2021.116156
PMID:33894508
Abstract

Prostate cancer (PCa) is one of the most common cancer types among men and also acommon cause of death globally. With an increasing incidence, there is aneed for low-cost, reliable biomarkers present in samples, which could be provided non-invasively (without a need to perform prostate biopsy). Glycosylation changes of free-PSA (fPSA) are considered cancer-specific, while the level of different PSA forms can increase under other than cancerous conditions. In the present study, we investigated the role ofN,N-diacetyllactosamine (LacdiNAc) epitope of fPSA (i.e. glycoprofile of fPSA or gPSA) in combination with total-PSA (tPSA), prostate volume, and tPSA density (tPSA level divided by prostate volume i.e. PSAd) as biomarkers for monitoring of PCa development and progression in 105 men. Furthermore, we applied an genetic (evolutionary) algorithm to identify any suspicious individuals in abenign cohort having benign prostatic hyperplasia (BPH). We identified 3 suspicious men originally diagnosed with BPH using gPSA analysis. In thefollow-up we found out that two men should not be considered as BPH patients since multiparametric magnetic resonance imaging (mpMRI) identified one man with clinically significant PCa via Prostate Imaging - Reporting and Data System (PI RADS v2 = 4) and the second man was with High-gradeprostatic intraepithelial neoplasia (HG PIN), commonly described as apre-cancerous stage. Moreover, in the study we described for the first time that changed LacdiNAc on PSA can be applied to identify prostatitis patients and most importantly this is the first study suggesting that changed glycosylation on PSA can be applied to identify castration-resistant prostate cancer (CRPCa) patients.

摘要

前列腺癌(PCa)是男性中最常见的癌症类型之一,也是全球范围内常见的死亡原因。随着发病率的增加,人们需要在样本中找到低成本、可靠的生物标志物,这些标志物可以通过非侵入性的方式(无需进行前列腺活检)提供。游离前列腺特异性抗原(fPSA)的糖基化变化被认为具有癌症特异性,而不同 PSA 形式的水平在非癌性情况下可能会升高。在本研究中,我们研究了 N,N-二乙酰乳糖胺(LacdiNAc)表位 fPSA(即 fPSA 的糖基化谱或 gPSA)与总 PSA(tPSA)、前列腺体积和 tPSA 密度(tPSA 水平除以前列腺体积,即 PSAd)相结合,作为监测 105 名男性 PCa 发展和进展的生物标志物的作用。此外,我们应用遗传(进化)算法来识别良性前列腺增生(BPH)良性队列中的可疑个体。我们通过 gPSA 分析确定了 3 名最初被诊断为 BPH 的可疑男性。在后续随访中,我们发现有 2 名男性不应被视为 BPH 患者,因为多参数磁共振成像(mpMRI)通过前列腺成像报告和数据系统(PI RADS v2 = 4)发现 1 名男性患有临床显著的 PCa,而另 1 名男性患有高级别前列腺上皮内瘤变(HG PIN),通常被描述为癌前阶段。此外,在这项研究中,我们首次描述了 PSA 上的 LacdiNAc 变化可用于识别前列腺炎患者,最重要的是,这是首次研究表明 PSA 上的糖基化变化可用于识别去势抵抗性前列腺癌(CRPCa)患者。

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Detection of N,N-diacetyllactosamine (LacdiNAc) containing free prostate-specific antigen for early stage prostate cancer diagnostics and for identification of castration-resistant prostate cancer patients.检测含有 N,N-二乙酰乳糖胺(LacdiNAc)的游离前列腺特异性抗原,用于早期前列腺癌诊断和识别去势抵抗性前列腺癌患者。
Bioorg Med Chem. 2021 Jun 1;39:116156. doi: 10.1016/j.bmc.2021.116156. Epub 2021 Apr 20.
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