Princeton Biochemicals, Inc., Princeton, NJ 08543, USA.
Division of Hospital Medicine, Department of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA.
Biomolecules. 2021 Oct 1;11(10):1443. doi: 10.3390/biom11101443.
Over the years, multiple biomarkers have been used to aid in disease screening, diagnosis, prognosis, and response to therapy. As of late, protein biomarkers are gaining strength in their role for early disease diagnosis and prognosis in part due to the advancements in identification and characterization of a distinct functional pool of proteins known as proteoforms. Proteoforms are defined as all of the different molecular forms of a protein derived from a single gene caused by genetic variations, alternative spliced RNA transcripts and post-translational modifications. Monitoring the structural changes of each proteoform of a particular protein is essential to elucidate the complex molecular mechanisms that guide the course of disease. Clinical proteomics therefore holds the potential to offer further insight into disease pathology, progression, and prevention. Nevertheless, more technologically advanced diagnostic methods are needed to improve the reliability and clinical applicability of proteomics in preventive medicine. In this manuscript, we review the use of immunoaffinity capillary electrophoresis (IACE) as an emerging powerful diagnostic tool to isolate, separate, detect and characterize proteoform biomarkers obtained from liquid biopsy. IACE is an affinity capture-separation technology capable of isolating, concentrating and analyzing a wide range of biomarkers present in biological fluids. Isolation and concentration of target analytes is accomplished through binding to one or more biorecognition affinity ligands immobilized to a solid support, while separation and analysis are achieved by high-resolution capillary electrophoresis (CE) coupled to one or more detectors. IACE has the potential to generate rapid results with significant accuracy, leading to reliability and reproducibility in diagnosing and monitoring disease. Additionally, IACE has the capability of monitoring the efficacy of therapeutic agents by quantifying companion and complementary protein biomarkers. With advancements in telemedicine and artificial intelligence, the implementation of proteoform biomarker detection and analysis may significantly improve our capacity to identify medical conditions early and intervene in ways that improve health outcomes for individuals and populations.
多年来，已经有多种生物标志物被用于辅助疾病的筛查、诊断、预后以及治疗反应的评估。最近，蛋白质生物标志物在疾病的早期诊断和预后中的作用越来越重要，部分原因是由于鉴定和描述一种独特的、功能明确的蛋白质称为蛋白质翻译后修饰体（proteoforms）的技术取得了进展。蛋白质翻译后修饰体被定义为从单个基因产生的蛋白质的所有不同分子形式，这些形式是由遗传变异、选择性剪接 RNA 转录本和翻译后修饰引起的。监测特定蛋白质的每种蛋白质翻译后修饰体的结构变化对于阐明指导疾病进程的复杂分子机制至关重要。因此，临床蛋白质组学有可能为疾病的病理、进展和预防提供进一步的深入了解。然而，需要更先进的技术诊断方法来提高蛋白质组学在预防医学中的可靠性和临床适用性。在本文中，我们回顾了免疫亲和毛细管电泳（IACE）作为一种新兴的强大诊断工具在分离、分离、检测和表征从液体活检中获得的蛋白质翻译后修饰体生物标志物的应用。IACE 是一种亲和捕获分离技术，能够分离、浓缩和分析生物体液中存在的多种生物标志物。通过将一个或多个生物识别亲和配体固定在固体载体上，实现对靶分析物的分离和浓缩，而通过高分辨率毛细管电泳（CE）与一个或多个检测器的联用，实现对分离和分析。IACE 具有生成快速、准确结果的潜力，从而提高诊断和监测疾病的可靠性和可重复性。此外，IACE 能够通过定量监测伴随和互补的蛋白质生物标志物来监测治疗药物的疗效。随着远程医疗和人工智能的进步，实施蛋白质翻译后修饰体生物标志物的检测和分析可能会显著提高我们早期识别医疗状况并采取措施改善个人和人群健康结果的能力。
