Department of Neurology, Tianjin First Central Hospital, Nankai District, Tianjin, China.
Int J Neurosci. 2020 Nov;130(11):1082-1094. doi: 10.1080/00207454.2020.1720677. Epub 2020 Feb 5.
Alzheimer's disease (AD) is a degenerative neurologic disease. The study aimed to identify the key differentially expressed genes (DEGs) and pathways in AD pathogenesis and obtain potential biomarkers in AD diagnosis. An integrated analysis of publicly available Gene Expression Omnibus datasets of AD was performed. DEGs in hippocampus tissue (HIP), temporal gyrus tissue (TG), frontal gyrus tissue (FG) and whole blood (WB) were identified. Bioinformatics analyses were used to insight into the functions of DEGs. The expression levels of candidate DEGs were preliminarily validated in GSE1297. The discriminatory ability of candidate DEGs in WB samples of AD patients and healthy individuals was evaluated in GSE63060 and GSE63061 datasets through receiver operating characteristic (ROC) analysis. The DEGs in HIP, TG and FG tissues of AD were identified. Functions involved in regulation of apoptotic process, apoptotic process and cell death were significantly enriched from DEGs in AD. MAPK signaling pathway and Wnt signaling pathway were significantly enriched. YAP1, MAPK9 and GJA1 were the hub proteins in protein-protein interaction network in HIP, TG and FG. The expression levels of 14 DEGs in GSE1297 dataset were consistent with our integrated analysis. Moreover, 7 out of 14 DEGs had the diagnostic value in distinguishing AD patients from healthy controls in both GSE630060 and GSE630061 datasets. The DEGs including YAP1, MAPK1, GJA1 and pathways including MAPK signaling pathway and Wnt signaling pathway may be related to AD progression. RAD51C, SAFB2, SSH3 and TXNDC9 might be potential biomarkers in AD diagnosis.
阿尔茨海默病（AD）是一种退行性神经疾病。本研究旨在鉴定 AD 发病机制中的关键差异表达基因（DEGs）和途径，并获得 AD 诊断的潜在生物标志物。对 AD 的公共可用基因表达综合分析数据集进行了分析。鉴定了海马组织（HIP）、颞叶组织（TG）、额叶组织（FG）和全血（WB）中的 DEGs。使用生物信息学分析深入研究 DEGs 的功能。在 GSE1297 中初步验证了候选 DEGs 的表达水平。通过接收者操作特征（ROC）分析，在 GSE63060 和 GSE63061 数据集中评估候选 DEGs 在 AD 患者和健康个体的 WB 样本中的区分能力。鉴定了 AD 患者 HIP、TG 和 FG 组织中的 DEGs。从 AD 的 DEGs 中显著富集了涉及凋亡过程调节、凋亡过程和细胞死亡的功能。MAPK 信号通路和 Wnt 信号通路显著富集。YAP1、MAPK9 和 GJA1 是 HIP、TG 和 FG 中蛋白质-蛋白质相互作用网络的枢纽蛋白。GSE1297 数据集中的 14 个 DEG 的表达水平与我们的综合分析一致。此外，在 GSE630060 和 GSE630061 数据集中，14 个 DEG 中有 7 个具有区分 AD 患者和健康对照的诊断价值。包括 YAP1、MAPK1、GJA1 和途径包括 MAPK 信号通路和 Wnt 信号通路的 DEGs 可能与 AD 的进展有关。RAD51C、SAFB2、SSH3 和 TXNDC9 可能是 AD 诊断的潜在生物标志物。
