通过蛋白质组学发现和验证肌萎缩侧索硬化症的生物标志物。
Discovery and verification of amyotrophic lateral sclerosis biomarkers by proteomics.
机构信息
Department of Pathology, University of Pittsburgh School of Medicine, BST S-420, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA.
出版信息
Muscle Nerve. 2010 Jul;42(1):104-11. doi: 10.1002/mus.21683.
Recent studies using mass spectrometry have discovered candidate biomarkers for amyotrophic lateral sclerosis (ALS). However, those studies utilized small numbers of ALS and control subjects. Additional studies using larger subject cohorts are required to verify these candidate biomarkers. Cerebrospinal fluid (CSF) samples from 100 patients with ALS, 100 disease control, and 41 healthy control subjects were examined by mass spectrometry. Sixty-one 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 posttranslational 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 enzyme-linked immunoassay. 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%.
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，这些研究使用的 ALS 和对照受试者数量较少。需要使用更大的受试者队列进行额外的研究来验证这些候选生物标志物。通过质谱法检查了 100 名 ALS 患者、100 名疾病对照和 41 名健康对照的脑脊液 (CSF) 样本。61 个质谱峰在 ALS 和对照组之间表现出改变的水平。胱抑素 C 和转甲状腺素的质量峰在 ALS 中减少，而翻译后修饰的转甲状腺素和 C 反应蛋白 (CRP) 的质量峰增加。通过酶联免疫吸附法测定，对照组的 CRP 水平为 5.84 +/- 1.01ng/ml，ALS 组为 11.24 +/- 1.52ng/ml。这项研究验证了先前在 ALS 中胱抑素 C 和转甲状腺素的质谱结果。在 ALS 患者的 CSF 中 CRP 水平升高，并且胱抑素 C 水平与肢体发病患者的生存相关。我们的生物标志物谱预测 ALS 的总体准确性为 82%。
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