Diagnostic models and predictive drugs associated with cuproptosis hub genes in Alzheimer's disease

Erdong Zhang; Fengqiu Dai; Tingting Chen; Shanhui Liu; Chaolun Xiao; Xiangchun Shen

doi:10.3389/fneur.2022.1064639

Diagnostic models and predictive drugs associated with cuproptosis hub genes in Alzheimer's disease

Front Neurol. 2023 Jan 26:13:1064639. doi: 10.3389/fneur.2022.1064639. eCollection 2022.

Authors

Erdong Zhang^{1

2}, Fengqiu Dai³, Tingting Chen⁴, Shanhui Liu⁵, Chaolun Xiao³, Xiangchun Shen^{1

2}

Affiliations

¹ State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou, China.
² Key Laboratory of Optimal Utilization of Natural Medicinal Resources, Guizhou Medical University, Guiyang, Guizhou, China.
³ Department of Anatomy, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.
⁴ Guiyang Maternal and Child Health-Care Hospital, Guiyang, Guizhou, China.
⁵ Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Institute of Urology, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disease, and its underlying genes and treatments are unclear. Abnormalities in copper metabolism can prevent the clearance of β-amyloid peptides and promote the progression of AD pathogenesis. Therefore, the present study used a bioinformatics approach to perform an integrated analysis of the hub gene based on cuproptosis that can influence the diagnosis and treatment of AD. The gene expression profiles were obtained from the Gene Expression Omnibus database, including non-demented (ND) and AD samples. A total of 2,977 cuproptosis genes were retrieved from published articles. The seven hub genes associated with cuproptosis and AD were obtained from the differentially expressed genes and WGCNA in brain tissue from GSE33000. The GO analysis demonstrated that these genes were involved in phosphoribosyl pyrophosphate, lipid, and glucose metabolism. By stepwise regression and logistic regression analysis, we screened four of the seven cuproptosis genes to construct a diagnostic model for AD, which was validated by GES15222, GS48350, and GSE5281. In addition, immune cell infiltration of samples was investigated for correlation with these hub genes. We identified six drugs targeting these seven cuproptosis genes in DrugBank. Hence, these cuproptosis gene signatures may be an important prognostic indicator for AD and may offer new insights into treatment options.

Keywords: Alzheimer's disease; cuproptosis; diagnostic; drug; immune.

Grants and funding

This study was supported by the Doctoral Scientific Research Foundation of Guizhou Medical University (No. YJ20066), the National Natural Science Foundation of China Cultivation Project of Guizhou Medical University (No. 20NSP051), the Scientific and Technological Project of Guizhou Province [No. ZK (2022) 398], and the Fund of Science and Technology Project of Guizhou provincial health commission (No. Gzwkj2023-564).