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基于iTRAQ的蛋白质组学分析揭示自闭症儿童血浆中的蛋白质谱。

iTRAQ-Based Proteomic Analysis Reveals Protein Profile in Plasma from Children with Autism.

作者信息

Shen Liming, Zhang Kaoyuan, Feng Chengyun, Chen Youjiao, Li Shuiming, Iqbal Javed, Liao Liping, Zhao Yuxi, Zhai Jian

机构信息

College of Life Science and Oceanography, Shenzhen University, Shenzhen, P. R. China.

Maternal and Child Health Hospital of Baoan, Shenzhen, P. R. China.

出版信息

Proteomics Clin Appl. 2018 May;12(3):e1700085. doi: 10.1002/prca.201700085. Epub 2018 Jan 18.

Abstract

PURPOSE

Autism is a childhood neurological disorder with poorly understood etiology and pathology. This study is designed to identify differentially expressed proteins that might serve as potential biomarkers for autism.

EXPERIMENTAL DESIGN

We perform iTRAQ (isobaric tags for relative and absolute quantitation) analysis for normal and autistic children's plasma of the same age group.

RESULTS

The results show that 24 differentially expressed proteins were identified between autistic subjects and controls. For the first time, differential expression of complement C5 (C5) and fermitin family homolog 3 (FERMT3) are related to autism. Five proteins, that is, complement C3 (C3), C5, integrin alpha-IIb (ITGA2B), talin-1 (TLN1), and vitamin D-binding protein (GC) were validated via enzyme-linked immunosorbent assay (ELISA). By ROC (receiver operating characteristic) analysis, combinations of these five proteins C3, C5, GC, ITGA2B, and TLN1 distinguished autistic children from healthy controls with a high AUC (area under the ROC curve) value (0.982, 95% CI, 0.957-1.000, p < 0.000).

CONCLUSION

These above described proteins are found involved in different pathways that have previously been linked to the pathophysiology of autism spectrum disorders (ASDs). The results strongly support that focal adhesions, acting cytoskeleton, cell adhesion, motility and migration, synaptogenesis, and complement system are involved in the pathogenesis of autism, and highlight the important role of platelet function in the pathophysiology of autism.

摘要

目的

自闭症是一种病因和病理机制尚不清楚的儿童神经疾病。本研究旨在鉴定可能作为自闭症潜在生物标志物的差异表达蛋白。

实验设计

我们对同一年龄组正常儿童和自闭症儿童的血浆进行了iTRAQ(相对和绝对定量等压标签)分析。

结果

结果显示,在自闭症受试者和对照组之间鉴定出24种差异表达蛋白。首次发现补体C5(C5)和费米汀家族同源物3(FERMT3)的差异表达与自闭症有关。通过酶联免疫吸附测定(ELISA)验证了5种蛋白,即补体C3(C3)、C5、整合素α-IIb(ITGA2B)、踝蛋白-1(TLN1)和维生素D结合蛋白(GC)。通过ROC(受试者工作特征)分析,这5种蛋白C3、C5、GC、ITGA2B和TLN1的组合区分自闭症儿童和健康对照的AUC(ROC曲线下面积)值较高(0.982,95%CI,0.957-1.000,p<0.000)。

结论

上述蛋白参与了先前与自闭症谱系障碍(ASD)病理生理学相关的不同途径。结果有力地支持了粘着斑、作用于细胞骨架、细胞粘附、运动和迁移、突触形成以及补体系统参与自闭症的发病机制,并突出了血小板功能在自闭症病理生理学中的重要作用。

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