Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, United States.
Division of Gastroenterology and Hepatology, University of Kansas Health System, Kansas City, KS, United States.
Clin Chem. 2024 Jan 4;70(1):206-219. doi: 10.1093/clinchem/hvad176.
Cancer is a dynamic process and thus requires highly informative and reliable biomarkers to help guide patient care. Liquid-based biopsies have emerged as a clinical tool for tracking cancer dynamics. Extracellular vesicles (EVs), lipid bilayer delimited particles secreted by cells, are a new class of liquid-based biomarkers. EVs are rich in selectively sorted biomolecule cargos, which provide a spatiotemporal fingerprint of the cell of origin, including cancer cells.
This review summarizes the performance characteristics of EV-based biomarkers at different stages of cancer progression, from early malignancy to recurrence, while emphasizing their potential as diagnostic, prognostic, and screening biomarkers. We discuss the characteristics of effective biomarkers, consider challenges associated with the EV biomarker field, and report guidelines based on the biomarker discovery pipeline.
Basic science and clinical trial studies have shown the potential of EVs as precision-based biomarkers for tracking cancer status, with promising applications for diagnosing disease, predicting response to therapy, and tracking disease burden. The multi-analyte cargos of EVs enhance the performance characteristics of biomarkers. Recent technological advances in ultrasensitive detection of EVs have shown promise with high specificity and sensitivity to differentiate early-cancer cases vs healthy individuals, potentially outperforming current gold-standard imaging-based cancer diagnosis. Ultimately, clinical translation will be dictated by how these new EV biomarker-based platforms perform in larger sample cohorts. Applying ultrasensitive, scalable, and reproducible EV detection platforms with better design considerations based upon the biomarker discovery pipeline should guide the field towards clinically useful liquid biopsy biomarkers.
癌症是一个动态的过程，因此需要高度信息丰富且可靠的生物标志物来帮助指导患者的护理。基于液体的活检已成为追踪癌症动态的临床工具。细胞分泌的双层膜囊泡（EVs）是一种新型的基于液体的生物标志物。EVs 富含选择性分拣的生物分子货物，提供了起源细胞的时空指纹，包括癌细胞。
本文综述了 EV 基生物标志物在癌症进展的不同阶段的性能特征，从早期恶性肿瘤到复发，同时强调了它们作为诊断、预后和筛查生物标志物的潜力。我们讨论了有效生物标志物的特征，考虑了 EV 生物标志物领域相关的挑战，并根据生物标志物发现管道报告了指南。
基础科学和临床试验研究表明，EV 作为基于精准医疗的生物标志物具有追踪癌症状态的潜力，在诊断疾病、预测治疗反应和跟踪疾病负担方面具有有前景的应用。EV 的多分析物货物增强了生物标志物的性能特征。最近，EV 超敏检测技术的进步显示出了很高的特异性和灵敏度，能够区分早期癌症病例与健康个体，有可能优于当前基于成像的金标准癌症诊断。最终，这些新的基于 EV 生物标志物的平台在更大的样本队列中的表现将决定其临床转化。应用超敏、可扩展和可重复的 EV 检测平台，并根据生物标志物发现管道更好地设计考虑因素，应指导该领域朝着具有临床应用价值的液体活检生物标志物发展。
