Centre for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology , University of Queensland , Brisbane , QLD 4072 , Australia.
The University of Queensland, Centre for Clinical Research , Brisbane , QLD 4029 , Australia.
ACS Nano. 2018 Aug 28;12(8):8362-8371. doi: 10.1021/acsnano.8b03698. Epub 2018 Jul 26.
The use of emerging nanotechnologies, such as plasmonic nanoparticles in diagnostic applications, potentially offers opportunities to revolutionize disease management and patient healthcare. Despite worldwide research efforts in this area, there is still a dearth of nanodiagnostics which have been successfully translated for real-world patient usage due to the predominant sole focus on assay analytical performance and lack of detailed investigations into clinical performance in human samples. In a bid to address this pressing need, we herein describe a comprehensive clinical verification of a prospective label-free surface-enhanced Raman scattering (SERS) nanodiagnostic assay for prostate cancer (PCa) risk stratification. This contribution depicts a roadmap of (1) designing a SERS assay for robust and accurate detection of clinically validated PCa RNA targets; (2) employing a relevant and proven PCa clinical biomarker model to test our nanodiagnostic assay; and (3) investigating the clinical performance on independent training ( n = 80) and validation ( n = 40) cohorts of PCa human patient samples. By relating the detection outcomes to gold-standard patient biopsy findings, we established a PCa risk scoring system which exhibited a clinical sensitivity and specificity of 0.87 and 0.90, respectively [area-under-curve of 0.84 (95% confidence interval: 0.81-0.87) for differentiating high- and low-risk PCa] in the validation cohort. We envision that our SERS nanodiagnostic design and clinical verification approach may aid in the individualized prediction of PCa presence and risk stratification and may overall serve as an archetypical strategy to encourage comprehensive clinical evaluation of nanodiagnostic innovations.
新兴纳米技术的应用，如等离子体纳米粒子在诊断应用中，有可能为疾病管理和患者医疗保健带来革命性的变化。尽管在这一领域进行了全球范围内的研究，但由于主要关注分析性能，并且缺乏对人体样本临床性能的详细研究，因此仍然缺乏成功转化为实际患者使用的纳米诊断方法。为了解决这一紧迫需求，我们在此描述了一种针对前列腺癌（PCa）风险分层的前瞻性无标记表面增强拉曼散射（SERS）纳米诊断检测的全面临床验证。本研究描绘了（1）设计用于稳健和准确检测经过临床验证的 PCa RNA 靶标的 SERS 检测方法；（2）采用相关且经过验证的 PCa 临床生物标志物模型来测试我们的纳米诊断检测方法；（3）在独立的训练（n = 80）和验证（n = 40）队列的 PCa 患者样本中研究临床性能。通过将检测结果与金标准患者活检结果相关联，我们建立了一个 PCa 风险评分系统，该系统在验证队列中显示出 0.87 的临床灵敏度和 0.90 的特异性[区分高低危 PCa 的曲线下面积为 0.84（95%置信区间：0.81-0.87）]。我们设想，我们的 SERS 纳米诊断设计和临床验证方法可以帮助预测 PCa 的存在和风险分层，并为鼓励全面评估纳米诊断创新提供一种典型策略。
