Dowling Paul, Negroni Elisa, Trollet Capucine, Zweyer Margit, Swandulla Dieter, Ohlendieck Kay
Department of Biology, Maynooth University, National University of Ireland, Maynooth, Co. Kildare, Ireland; Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Co. Kildare.
Centre for Research in Myology U974, Sorbonne Université, INSERM, Myology Institute, Paris.
Eur J Transl Myol. 2025 Jun 27;35(2). doi: 10.4081/ejtm.2025.13956. Epub 2025 May 28.
In contrast to invasive skeletal muscle biopsies and the associated complexity of tissue sampling techniques and potential detrimental side effects, the alternative application of liquid biopsy procedures has considerable advantages concerning minimal invasiveness, repeated sampling options, assay robustness and cost effectiveness. This article outlines the current status of serum biomarkers used for diagnosing and characterizing Duchenne muscular dystrophy (DMD), a primary muscle wasting disease of early childhood due to primary abnormalities in the extremely large DMD gene. Reviewed are important aspects of the discovery, characterization and diagnostic value of biofluid-based protein markers of dystrophinopathy. This includes an overview of traditional general skeletal muscle damage markers, such as creatine kinase, myoglobin and lactate dehydrogenase, which have been used for many decades in clinical applications to evaluate patients with muscular weakness. In addition, this article outlines the biochemical identification of novel biomarker candidates focusing on the usage of mass spectrometry-based proteomic surveys to establish comprehensive profiles of protein alterations in dystrophinopathy. Pathoproteomic serum markers of myonecrosis with great potential for improved patient screening, differential diagnosis, stage-specific prognosis and therapeutic monitoring include specific isoforms of muscle-derived cytosolic proteins, such as carbonic anhydrase isoform CA3 and fatty acid binding protein FABP3, as well as sarcomeric proteins, including specific isoforms of myosin light chain, myosin binding protein, troponin, and myomesin, in addition to peptide fragments derived from the giant protein titin. Biofluid-associated marker proteins of reactive myofibrosis include the extracellular matrix proteins fibronectin, osteopontin, collagen and matrix-metalloproteinases.
与侵入性骨骼肌活检以及相关的组织采样技术复杂性和潜在有害副作用形成对比的是，液体活检程序的另一种应用在微创性、重复采样选择、检测稳健性和成本效益方面具有相当大的优势。本文概述了用于诊断和表征杜兴氏肌营养不良症（DMD）的血清生物标志物的现状，DMD是一种儿童早期的原发性肌肉萎缩疾病，病因是超大的DMD基因存在原发性异常。本文回顾了基于生物流体的肌营养不良蛋白病蛋白质标志物的发现、表征和诊断价值的重要方面。这包括对传统的一般骨骼肌损伤标志物的概述，如肌酸激酶、肌红蛋白和乳酸脱氢酶，这些标志物在临床应用中已使用数十年，用于评估肌无力患者。此外，本文概述了新型生物标志物候选物的生化鉴定，重点是基于质谱的蛋白质组学调查的应用，以建立肌营养不良蛋白病中蛋白质改变的综合概况。具有改善患者筛查、鉴别诊断、阶段特异性预后和治疗监测潜力的肌坏死病理蛋白质组学血清标志物包括肌肉来源的胞质蛋白的特定异构体，如碳酸酐酶异构体CA3和脂肪酸结合蛋白FABP3，以及肌节蛋白，包括肌球蛋白轻链、肌球蛋白结合蛋白、肌钙蛋白和肌间蛋白的特定异构体，此外还有来自巨大蛋白肌联蛋白的肽片段。反应性肌纤维化的生物流体相关标志物蛋白包括细胞外基质蛋白纤连蛋白、骨桥蛋白、胶原蛋白和基质金属蛋白酶。
