Differential Expression of mRNAs in the Brain Tissues of Patients with Alzheimer's Disease Based on GEO Expression Profile and Its Clinical Significance
Differential Expression of mRNAs in the Brain Tissues of Patients with Alzheimer's Disease Based on GEO Expression Profile and Its Clinical Significance
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DOI：
10.1155/2019/8179145
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Wei, Minjie
中科院分区：
文献类型：
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作者：
Ma, Guowei;Liu, Mingyan;Wei, Minjie
背景阿尔茨海默病（Alzheimer's disease，AD）的早期诊断是AD防治的当务之急。AD的生物标志物仍不明确。本研究通过对阿尔茨海默病（Alzheimer's disease，AD）患者脑组织和外周血中mRNA差异表达的生物信息学分析，寻找可作为AD生物标志物的靶mRNA，并建立一种新的有效、实用的临床检测方案。方法.在本研究中，我们将AD外周血单核细胞（PBMC）表达数据集（GEO登记号GSE 4226和GSE 18309）与来自GEO的AD脑组织表达数据集（GEO登记号GSE 1297和GSE 5281）进行了比较。利用GEO基因数据库下载相应的基因表达谱，分析AD患者和正常老年人脑组织和血液中mRNA的差异表达。应用维恩图筛选出脑组织和血液中mRNA的差异表达。蛋白质相互作用网络图（PPI）用于查看可能基因之间的相关性。GO（gene ontology）和KEGG（京都基因和基因组百科全书）用于基因富集分析以确定主要受影响的基因和功能或途径。结果生物信息学分析显示，AD患者外周血和海马中存在差异表达基因。AD患者与健康老年人相比，GSE 18309、GSE 4226、GSE 5281和GSE 129的mRNA差异分别为4958、577、7464和317条。筛选海马和外周血中共表达的RAB 7A和ITGB 1两种mRNA。通过PPI网络图、GO和KEGG分析，进一步丰富了差异基因的功能，最终分别找出趋化性、粘附性和炎症反应。结论.海马和PBMCs中ITGB 1和RAB 7A mRNA的表达均发生变化，提示ITGB 1和RAB 7A可作为AD的生物标志物。同时，根据这一分析结果表明，我们可以以6个月或1年的频率检测老年人的血常规2-3年。当患者持续检测到炎症表现时，其被指示为潜在的高风险AD患者以进行AD预防。
Background. Early diagnosis of Alzheimer's disease (AD) is an urgent point for AD prevention and treatment. The biomarkers of AD still remain indefinite. Based on the bioinformatics analysis of mRNA differential expressions in the brain tissues and the peripheral blood samples of Alzheimer's disease (AD) patients, we investigated the target mRNAs that could be used as an AD biomarker and developed a new effective, practical clinical examination program. Methods. We compared the AD peripheral blood mononuclear cells (PBMCs) expression dataset (GEO accession GSE4226 and GSE18309) with AD brain tissue expression datasets (GEO accessions GSE1297 and GSE5281) from GEO in the present study. The GEO gene database was used to download the appropriate gene expression profiles to analyze the differential mRNA expressions between brain tissue and blood of AD patients and normal elderly. The Venn diagram was used to screen out the differential expression of mRNAs between the brain tissue and blood. The protein-protein interaction network map (PPI) was used to view the correlation between the possible genes. GO (gene ontology) and KEGG (Kyoto Gene and Genomic Encyclopedia) were used for gene enrichment analysis to determine the major affected genes and the function or pathway. Results. Bioinformatics analysis revealed that there were differentially expressed genes in peripheral blood and hippocampus of AD patients. There were 4958 differential mRNAs in GSE18309, 577 differential mRNAs in GSE4226 in AD PBMCs sample, 7464 differential mRNAs in GSE5281, and 317 differential mRNAs in GSE129 in AD brain tissues, when comparing between AD patients and healthy elderly. Two mRNAs of RAB7A and ITGB1 coexpressed in hippocampus and peripheral blood were screened. Furthermore, functions of differential genes were enriched by the PPI network map, GO, and KEGG analysis, and finally the chemotaxis, adhesion, and inflammatory reactions were found out, respectively. Conclusions. ITGB1 and RAB7A mRNA expressions were both changed in hippocampus and PBMCs, highly suggested being used as an AD biomarker with AD. Also, according to the results of this analysis, it is indicated that we can test the blood routine of the elderly for 2-3 years at a frequency of 6 months or one year. When a patient continuously detects the inflammatory manifestations, it is indicated as a potentially high-risk AD patient for AD prevention.