Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy.
Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy.
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DOI：
10.1073/pnas.1507719112
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发表时间：
2015-06-09
影响因子：
11.1
通讯作者：
Gold L
中科院分区：
文献类型：
--
作者：
Hathout Y;Brody E;Clemens PR;Cripe L;DeLisle RK;Furlong P;Gordish-Dressman H;Hache L;Henricson E;Hoffman EP;Kobayashi YM;Lorts A;Mah JK;McDonald C;Mehler B;Nelson S;Nikrad M;Singer B;Steele F;Sterling D;Sweeney HL;Williams S;Gold L
杜氏肌营养不良症（DMD）是一种罕见的、毁灭性的肌肉疾病，由x连锁的DMD基因（编码肌营养不良蛋白）突变引起。血清生物标志物作为DMD疾病状态的客观表型指标，以及治疗干预的药理作用和反应的潜在指标，具有重要的潜力。在这里，我们描述了一种蛋白质组学方法来测定93名DMD患者和45名对照组的1125种蛋白质的血清水平。该研究确定了44种生物标志物，在患者和对照组之间存在显著差异。这些数据正在提供给DMD研究人员和临床医生，以加速寻找新的诊断、预后和治疗方法。杜氏肌营养不良症（DMD）的血清生物标志物可能为疾病发病机制提供更深入的见解，提出新的治疗方法，作为药物效应的急性读数，并可作为预测后期临床获益的替代结果指标。在这项研究中，使用改良的适配体蛋白质组学技术，对DMD患者和年龄匹配的健康志愿者的血清样本进行了大规模的生物标志物发现。对来自两个独立的DMD队列的血清样本中1125种蛋白的水平进行了量化：队列1 (The Parent Project Muscular Dystrophy-Cincinnati Children 's Hospital Medical Center)， 42名DMD患者和28名年龄匹配的正常志愿者；和队列2（国际神经肌肉合作研究小组，杜氏自然历史研究），51名DMD患者和17名年龄匹配的正常志愿者。在1%的错误发现率下，比较DMD患者和健康志愿者时，两个队列中有44种蛋白质显示出显著差异，这对于这样一个小研究来说是大量显著的蛋白质变化。这些生物标志物可以通过已知的细胞过程和蛋白质浓度的年龄依赖性变化进行分类。我们的研究结果证明了这种无偏倚的生物标志物发现方法的实用性，并为改善DMD负担以及我们希望的其他罕见和破坏性疾病提供了潜在的新诊断和治疗途径。
Duchenne muscular dystrophy (DMD) is a rare and devastating muscle disease caused by mutations in the X-linked DMD gene (which encodes the dystrophin protein). Serum biomarkers hold significant potential as objective phenotypic measures of DMD disease state, as well as potential measures of pharmacological effects of and response to therapeutic interventions. Here we describe a proteomics approach to determine serum levels of 1,125 proteins in 93 DMD patients and 45 controls. The study identified 44 biomarkers that differed significantly between patients and controls. These data are being made available to DMD researchers and clinicians to accelerate the search for new diagnostic, prognostic, and therapeutic approaches. Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy–Cincinnati Children’s Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and healthy volunteers at a 1% false-discovery rate, a large number of significant protein changes for such a small study. These biomarkers can be classified by known cellular processes and by age-dependent changes in protein concentration. Our findings demonstrate both the utility of this unbiased biomarker discovery approach and suggest potential new diagnostic and therapeutic avenues for ameliorating the burden of DMD and, we hope, other rare and devastating diseases.
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DOI：
10.1083/jcb.122.4.809
发表时间：
1993-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ervasti JM;Campbell KP
通讯作者：
Campbell KP
影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
158.5
作者：
Goemans, Nathalie M.;Tulinius, Mar;van Deutekom, Judith C.
通讯作者：
van Deutekom, Judith C.
DOI：
10.1016/j.pmr.2012.08.003
发表时间：
2012-11-01
影响因子：
1.7
作者：
Hoffman, Eric P.;Reeves, Erica;Bushby, Kate
通讯作者：
Bushby, Kate
影响因子：
168.9
作者：
Cirak, Sebahattin;Arechavala-Gomeza, Virginia;Guglieri, Michela;Feng, Lucy;Torelli, Silvia;Anthony, Karen;Abbs, Stephen;Garralda, Maria Elena;Bourke, John;Wells, Dominic J.;Dickson, George;Wood, Matthew J. A.;Wilton, Steve D.;Straub, Volker;Kole, Ryszard;Shrewsbury, Stephen B.;Sewry, Caroline;Morgan, Jennifer E.;Bushby, Kate;Muntoni, Francesco
通讯作者：
Muntoni, Francesco