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Multiplex Determination of Glycan Profiles on Urinary Prostate-Specific Antigen by Quartz-Crystal Microbalance Combined with Surface-Enhanced Raman Scattering
ACS Sensors ( IF 8.2 ) Pub Date : 2024-08-30 , DOI: 10.1021/acssensors.4c01252
Laura Armero 1, 2 , Javier Plou 1, 3, 4 , Pablo S Valera 1, 2, 4, 5 , Sonia Serna 1 , Isabel García 1, 4 , Luis M Liz-Marzán 1, 4, 6, 7
Affiliation  

Prostate cancer remains a major health concern, with prostate-specific antigen (PSA) being a key biomarker for its detection and monitoring. However, PSA levels often fall into a “gray zone”, where PSA levels are not clearly indicative of cancer, thus complicating early diagnosis and treatment decisions. Glycosylation profiles, which often differ between healthy and diseased cells, have emerged as potential biomarkers to enhance the specificity and sensitivity of cancer diagnosis in these ambiguous cases. We propose the integration of two complementary techniques, namely quartz-crystal microbalance with dissipation (QCM-D) and surface-enhanced Raman scattering (SERS) to study PSA glycan profiles. QCM-D offers real-time operation, PSA mass quantification, and label-free detection with high sensitivity, as well as enhanced specificity and reduced cross-reactivity when using nucleic acid aptamers as capture ligands. Complementary SERS sensing enables the determination of the glycosylation pattern on PSA, at low concentrations and without the drawbacks of photobleaching, thereby facilitating multiplexed glycosylation pattern analysis. This integrated setup could retrieve a data set comprising analyte concentrations and associated glycan profiles in relevant biological samples, which may eventually improve early disease detection and monitoring. Prostate-specific antigen (PSA), a glycoprotein secreted by prostate epithelial cells, serves as our proof-of-concept analyte. Our platform allows multiplex targeting of PSA multiplex glycosylation profiles of PSA at “gray zone” concentrations for prostate cancer diagnosis. We additionally show the use of SERS for glycan analysis in PSA secreted from prostate cancer cell lines after androgen-based treatment. Differences in PSA glycan profiles from resistant cell lines after androgen-based treatment may eventually improve cancer treatment.

中文翻译:


通过石英晶体微量天平结合表面增强拉曼散射对尿前列腺特异性抗原上的游离寡糖谱进行多重测定



前列腺癌仍然是一个主要的健康问题,前列腺特异性抗原 (PSA) 是其检测和监测的关键生物标志物。然而,PSA 水平通常属于“灰色地带”,即 PSA 水平并不明确表明癌症,从而使早期诊断和治疗决策复杂化。糖基化谱在健康细胞和患病细胞之间通常不同,已成为在这些模棱两可的病例中提高癌症诊断特异性和敏感性的潜在生物标志物。我们建议集成两种互补技术,即耗散石英晶体微天平 (QCM-D) 和表面增强拉曼散射 (SERS) 来研究 PSA 聚糖谱。QCM-D 提供实时操作、PSA 质量定量和无标记检测,灵敏度高,在使用核酸适配体作为捕获配体时,具有增强的特异性和更低的交叉反应性。互补的 SERS 传感能够在低浓度下测定 PSA 上的糖基化模式,并且没有光漂白的缺点,从而有助于多路复用糖基化模式分析。这种集成设置可以检索包含相关生物样品中分析物浓度和相关聚糖谱的数据集,最终可能会改善早期疾病检测和监测。前列腺特异性抗原 (PSA) 是一种由前列腺上皮细胞分泌的糖蛋白,可作为我们的概念验证分析物。我们的平台允许在“灰色区域”浓度下对 PSA 的多重糖基化曲线进行多重靶向,用于前列腺癌诊断。我们还展示了在基于雄激素的治疗后,使用 SERS 对前列腺癌细胞系分泌的 PSA 进行聚糖分析。 基于雄激素的治疗后耐药细胞系的 PSA 聚糖谱差异最终可能会改善癌症治疗。
更新日期:2024-08-30
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