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基于加权共表达网络分析和构建蛋白质-蛋白质相互作用鉴定额叶和颞叶皮质中血管性痴呆和阿尔茨海默病的枢纽基因。

Identification of vascular dementia and Alzheimer's disease hub genes expressed in the frontal lobe and temporal cortex by weighted co-expression network analysis and construction of a protein-protein interaction.

机构信息

Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, P.R. China.

Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan, P.R. China.

出版信息

Int J Neurosci. 2022 Oct;132(10):1049-1060. doi: 10.1080/00207454.2020.1860966. Epub 2021 Jan 18.

DOI:10.1080/00207454.2020.1860966
PMID:33401985
Abstract

It is difficult to distinguish cognitive decline due to AD from that sustained by cerebrovascular disease in view of the great overlap. It is uncertain in the molecular biological pathway behind AD and VaD. Our study aimed to explore the hub molecules and their associations with each other to identify potential biomarkers and therapeutic targets for the AD and VaD.Methods: We screened the differentially expressed genes of AD and VaD, used weighted gene co-expression network analysis and then constructed a VaD-AD-specific protein-protein interaction network with functional annotation to their related metabolic pathways. Finally, we performed a ROC curve analysis of hub proteins to get an idea about their diagnostic value. In the frontal lobe and temporal cortex, hub genes were identified. With regard to VaD, there were only three hub genes which encoded the neuropeptides, and The AUC of these genes were 0.804, 0.768 and 0.779, respectively. One signature was established for these three hub genes with AUC of 0.990. For the identification of AD and VaD, all hub genes were receptors. These genes included and . The AUC of these genes were 0.853, 0.859, 0.796, 0.775, 0.706, 0.677, 0.696, 0.668 and 0.652, respectively. The other signature was built for eleven hub genes with AUC of 0.990. In the frontal lobe and temporal cortex regions, hub genes are used as diagnostic markers, which may provide insight into personalized potential biomarkers and therapeutic targets for patients with VaD and AD.

摘要

鉴于两者之间存在很大的重叠,因此很难将 AD 导致的认知能力下降与由脑血管疾病引起的认知能力下降区分开来。AD 和 VaD 的分子生物学途径尚不确定。我们的研究旨在探索枢纽分子及其相互关系,以确定 AD 和 VaD 的潜在生物标志物和治疗靶点。

方法

我们筛选了 AD 和 VaD 的差异表达基因,使用加权基因共表达网络分析,然后构建了一个具有功能注释的 VaD-AD 特异性蛋白质-蛋白质相互作用网络及其相关代谢途径。最后,我们对枢纽蛋白进行 ROC 曲线分析,以了解其诊断价值。在前额叶和颞叶皮层中鉴定出枢纽基因。对于 VaD,只有三个枢纽基因编码神经肽,分别为 和 。这些基因的 AUC 分别为 0.804、0.768 和 0.779。这三个枢纽基因的 AUC 为 0.990,建立了一个特征。对于 AD 和 VaD 的识别,所有枢纽基因都是受体。这些基因包括 和 。这些基因的 AUC 分别为 0.853、0.859、0.796、0.775、0.706、0.677、0.696、0.668 和 0.652。对于十一个枢纽基因的 AUC 为 0.990,建立了另一个特征。在前额叶和颞叶皮层区域,枢纽基因可用作诊断标志物,这可能为 VaD 和 AD 患者的个性化潜在生物标志物和治疗靶点提供深入了解。

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