Disease-specific and glucocorticoid-responsive serum biomarkers for Duchenne Muscular Dystrophy
Disease-specific and glucocorticoid-responsive serum biomarkers for Duchenne Muscular Dystrophy
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DOI：
10.1038/s41598-019-48548-9
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发表时间：
2019-08-21
影响因子：
4.6
通讯作者：
McDonald, Craig
中科院分区：
文献类型：
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作者：
Hathout, Yetrib;Liang, Chen;McDonald, Craig
在过去的7年中，DMD的生物标志物被广泛发现，并且在独立的队列和不同的实验室中证实了大量这些生物标志物。在这些先前的研究中，糖皮质激素和年龄是两个主要的混杂变量。在这项新的研究中，使用SomaScan技术，并专注于尚未接受糖皮质激素治疗的年轻DMD患者的子集，我们确定了DMD中相对于年龄匹配的健康对照组的108种升高和70种降低的蛋白质（调整多重测试后p值< 0.05）。大多数升高的蛋白质是肌肉中心的，其次是细胞粘附、细胞外基质蛋白和少数促炎蛋白。减少的蛋白质大多数是细胞粘附蛋白，但也有一些与细胞分化和生长因子有关。糖皮质激素对这组DMD患者的后续治疗影响了两组主要的药效学生物标志物。第一组由80种血清蛋白组成，这些蛋白与DMD无关，并且在糖皮质激素治疗后降低或升高，因此反映了糖皮质激素的更广泛作用。第二组由17种与DMD相关的血清蛋白组成，这些蛋白在治疗下趋于正常化，从而反映了糖皮质激素治疗DMD的生理效应。总之，我们已经确定了多种循环蛋白质生物标志物，反映了DMD发病机制和糖皮质激素反应的复杂性。
Extensive biomarker discoveries for DMD have occurred in the past 7 years, and a vast array of these biomarkers were confirmed in independent cohorts and across different laboratories. In these previous studies, glucocorticoids and age were two major confounding variables. In this new study, using SomaScan technology and focusing on a subset of young DMD patients who were not yet treated with glucocorticoids, we identified 108 elevated and 70 decreased proteins in DMD relative to age matched healthy controls (p value < 0.05 after adjusting for multiple testing). The majority of the elevated proteins were muscle centric followed by cell adhesion, extracellular matrix proteins and a few pro-inflammatory proteins. The majority of decreased proteins were of cell adhesion, however, some had to do with cell differentiation and growth factors. Subsequent treatment of this group of DMD patients with glucocorticoids affected two major groups of pharmacodynamic biomarkers. The first group consisted of 80 serum proteins that were not associated with DMD and either decreased or increased following treatment with glucocorticoids, and therefore were reflective of a broader effect of glucocorticoids. The second group consisted of 17 serum proteins that were associated with DMD and these tended to normalize under treatment, thus reflecting physiologic effects of glucocorticoid treatment in DMD. In summary, we have identified a variety of circulating protein biomarkers that reflect the complex nature of DMD pathogenesis and response to glucocorticoids.