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Development of a glycoproteomic strategy to detect more aggressive prostate cancer using lectin-immunoassays for serum fucosylated PSA.
Clinical Proteomics ( IF 2.8 ) Pub Date : 2019-04-06 , DOI: 10.1186/s12014-019-9234-4
Ce Wang 1, 2 , Naseruddin Höti 1 , Tung-Shing Mamie Lih 1 , Lori J Sokoll 1 , Rui Zhang 1 , Zhen Zhang 1 , Hui Zhang 1 , Daniel W Chan 1
Affiliation  

Background Prostate-specific antigen (PSA) is commonly used as a serum biomarker for the detection of prostate cancer. However, levels of PSA in serum do not reliably distinguish aggressive prostate cancer from non-aggressive disease. Therefore, there is an urgent need for biomarkers that can differentiate aggressive prostate cancers from non-aggressive phenotypes. Fucosylation is one of the glycosylation-based protein modifications. Previously we demonstrated increased levels of serum fucosylated PSA in patients with aggressive prostate cancer using lectin selection followed by PSA immunoassay. Methods We developed two lectin-immunoassays, Lens culinaris agglutinin (LCA) and Aleuria aurantia lectin (AAL) followed by clinical PSA immunoassay and investigated the levels of PSA and its fucosylated glycoforms in serum specimens from prostate cancer patients with different Gleason scores. First, we developed standard curves for lectins enrichment, which were applied to lectin-immunoassay for fucosylated PSA-LCA and PSA-AAL quantification in serum samples. Results Our results showed that both LCA- and AAL-immunoassays detected elevated fucosylated PSA and were correlated with higher Gleason scores but only AAL-immunoassay detected an increased percentage of fucosylated PSA in patient serum with higher Gleason scores. Conclusion We have developed quantitative lectin-immunoassays for serum fucosylated PSA. Our data demonstrated that fucosylated PSA-AAL, % fucosylated PSA-AAL and fucosylated PSA-LCA levels could be effective biomarkers to differentiate aggressive prostate cancer [especially Gleason 7 (4 + 3) or above] from non-aggressive disease. We believe that application of these lectin-immunoassays to a larger patient population is needed to evaluate the clinical utilities of fucosylated PSA using AAL-PSA and LCA-PSA for aggressive prostate cancer.

中文翻译:

使用凝集素免疫测定法检测血清岩藻糖基化 PSA 的糖蛋白组学策略以检测更具侵袭性的前列腺癌。

背景 前列腺特异性抗原 (PSA) 通常用作检测前列腺癌的血清生物标志物。然而,血清中的 PSA 水平并不能可靠地区分侵袭性前列腺癌和非侵袭性疾病。因此,迫切需要能够区分侵袭性前列腺癌和非侵袭性表型的生物标志物。岩藻糖基化是基于糖基化的蛋白质修饰之一。以前,我们使用凝集素选择和 PSA 免疫测定证明了侵袭性前列腺癌患者血清岩藻糖基化 PSA 水平升高。方法 我们开发了两种凝集素免疫测定法,晶状体凝集素 (LCA) 和苦橙凝集素 (AAL),然后进行临床 PSA 免疫测定,并研究了不同 Gleason 评分的前列腺癌患者血清标本中 PSA 及其岩藻糖基化糖型的水平。首先,我们开发了凝集素富集的标准曲线,将其应用于凝集素免疫测定,用于血清样品中岩藻糖基化 PSA-LCA 和 PSA-AAL 的定量。结果 我们的结果表明,LCA 和 AAL 免疫测定均检测到岩藻糖基化 PSA 升高,并与较高的 Gleason 评分相关,但只有 AAL 免疫测定检测到患者血清中岩藻糖基化 PSA 的百分比增加,且 Gleason 评分较高。结论 我们开发了用于血清岩藻糖基化 PSA 的定量凝集素免疫测定法。我们的数据表明,岩藻糖基化的 PSA-AAL,岩藻糖基化 PSA-AAL 百分比和岩藻糖基化 PSA-LCA 水平可能是区分侵袭性前列腺癌 [特别是 Gleason 7 (4 + 3) 或以上] 与非侵袭性疾病的有效生物标志物。我们认为,需要将这些凝集素免疫测定法应用于更大的患者群体,以评估使用 AAL-PSA 和 LCA-PSA 的岩藻糖基化 PSA 对侵袭性前列腺癌的临床效用。
更新日期:2020-04-22
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