Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics.
Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics.
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DOI：
10.1002/mus.21683
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发表时间：
2010-07
期刊：
影响因子：
3.4
通讯作者：
Bowser, Robert
中科院分区：
文献类型：
--
作者：
Ryberg, Henrik;An, Jiyan;Darko, Samuel;Lustgarten, Jonathan Llyle;Jaffa, Matt;Gopalakrishnan, Vanathi;Lacomis, David;Cudkowicz, Merit;Bowser, Robert
最近使用质谱的研究发现了肌萎缩侧索硬化症（ALS）的候选生物标志物。然而，这些研究使用少量ALS和对照受试者。需要使用更大受试者队列的额外研究来验证这些候选生物标志物。用质谱法检测了100例ALS患者、100例疾病对照组和41例健康对照组的脑脊液（CSF）。61个质谱峰在ALS和对照之间表现出改变的水平。肌萎缩侧索硬化患者胱抑素C和甲状腺素运载蛋白的质量峰降低，而翻译后修饰的甲状腺素运载蛋白和C反应蛋白（CRP）的质量峰增加。通过ELISA测定，对照组的CRP水平为5.84±1.01 ng/mL，ALS受试者的CRP水平为11.24±1.52 ng/mL。本研究验证了ALS中半胱氨酸蛋白酶抑制剂C和甲状腺素运载蛋白的先前质谱结果。ALS患者CSF中CRP水平升高，而Cystatin C水平与肢体发病患者的生存相关。我们的生物标志物小组预测ALS的总体准确率为82%。
Recent studies using mass spectrometry have discovered candidate biomarkers for amyotrophic lateral sclerosis (ALS). However these studies utilize small numbers of ALS and control subjects. Additional studies using larger subject cohorts are required to verify these candidate biomarkers. Cerebrospinal fluid (CSF) from 100 patients with ALS, 100 disease control and 41 healthy control subjects were examined by mass spectrometry. 61 mass spectral peaks exhibited altered levels between ALS and controls. Mass peaks for cystatin C and transthyretin were reduced in ALS, whereas mass peaks for post-translational modified transthyretin and C-reactive protein (CRP) were increased. CRP levels were 5.84±1.01 ng/mL for controls and 11.24±1.52 ng/mL for ALS subjects as determined by ELISA. This study verified prior mass spectrometry results for cystatin C and transthyretin in ALS. CRP levels were increased in the CSF of ALS patients, and cystatin C level correlated with survival in patients with limb-onset disease. Our biomarker panel predicted ALS with an overall accuracy of 82%.
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