Affiliations: [a] Department of Neurology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, People’s Republic of China
| [b] Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
| [c] Department of Neurology (Cognitive sleep ward), Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
Correspondence:
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Correspondence to: Yifeng Du, MD, PhD, Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 324 Jingwuweiqi Road, Jinan, Shandong 250021, China. E-mail: duyifeng2013@163.com.
Note: [1] These authors contributed equally to this work.
Abstract: Background:Alzheimer’s disease (AD) brings heavy burden to society and family. There is an urgent need to find effective methods for disease diagnosis and treatment. The robust rank aggregation (RRA) approach that could aggregate the resulting gene lists has been widely utilized in genomic data analysis. Objective:To identify hub genes using RRA approach in AD. Methods:Seven microarray datasets in frontal cortex from GEO database were used to identify differential expressed genes (DEGs) in AD patients using RRA approach. STRING was performed to explore the protein-to-protein interaction (PPI). Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were utilized for enrichment analysis. Human Gene Connectome and Gene Set Enrichment Analysis were used for functional annotation. Finally, the expression levels of hub genes were validated in the cortex of 5xFAD mice by quantitative real-time polymerase chain reaction. Results:After RRA analysis, 473 DEGs (216 upregulated and 257 downregulated) were identified in AD samples. PPI showed that DEGs had a total of 416 nodes and 2750 edges. These genes were divided into 17 clusters, each of which contains at least three genes. After functional annotation and enrichment analysis, TAC1 is identified as the hub gene and may be related to synaptic function and inflammation. In addition, Tac1 was found downregulated in cortices of 5xFAD mice. Conclusion:In the current study, TAC1 is identified as a key gene in the frontal cortex of AD, providing insight into the possible pathogenesis and potential therapeutic targets for this disease.
