Ferroptosis-related biomarkers for Alzheimer's disease: Identification by bioinformatic analysis in hippocampus

Binyang Wang; Chenyang Fu; Yuanyuan Wei; Bonan Xu; Rongxing Yang; Chuanxiong Li; Meihua Qiu; Yong Yin; Dongdong Qin

doi:10.3389/fncel.2022.1023947

Ferroptosis-related biomarkers for Alzheimer's disease: Identification by bioinformatic analysis in hippocampus

Front Cell Neurosci. 2022 Nov 16:16:1023947. doi: 10.3389/fncel.2022.1023947. eCollection 2022.

Authors

Binyang Wang¹, Chenyang Fu², Yuanyuan Wei², Bonan Xu², Rongxing Yang¹, Chuanxiong Li¹, Meihua Qiu¹, Yong Yin¹, Dongdong Qin²

Affiliations

¹ Department of Rehabilitation Medicine, The Affiliated Hospital of Yunnan University, Kunming, China.
² School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, China.

Abstract

Background: Globally, Alzheimer's Disease (AD) accounts for the majority of dementia, making it a public health concern. AD treatment is limited due to the limited understanding of its pathogenesis. Recently, more and more evidence shows that ferroptosis lead to cell death in the brain, especially in the regions of the brain related to dementia.

Materials and methods: Three microarray datasets (GSE5281, GSE9770, GSE28146) related to AD were downloaded from Gene Expression Omnibus (GEO) datasets. Ferroptosis-related genes were extracted from FerrDb database. Data sets were separated into two groups. GSE5281 and GSE9770 were used to identify ferroptosis-related genes, and GSE28146 was used to verify results. During these processes, protein-protein interaction (PPI), the Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Finally, the differentiated values of ferroptosis-related genes were determined by receiver operator characteristic (ROC) monofactor analysis to judge their potential quality as biomarkers.

Results: Twenty-four ferroptosis-related genes were obtained. Using STRING (https://cn.string-db.org/) and Cytoscape with CytoHubba, the top 10 genes (RB1, AGPAT3, SESN2, KLHL24, ALOX15B, CA9, GDF15, DPP4, PRDX1, UBC, FTH1, ASNS, GOT1, PGD, ATG16L1, SLC3A2, DDIT3, RPL8, VDAC2, GLS2, MTOR, HSF1, AKR1C3, NCF2) were identified as target genes. GO analysis revealed that response to carboxylic acid catabolic process, organic acid catabolic process, alpha-amino acid biosynthetic process and cellular amino acid biosynthetic process were the most highly enriched terms. KEGG analysis showed that these overlapped genes were enriched in p53 signaling pathways, longevity regulating pathway, mTOR signaling pathway, type 2 diabetes mellitus and ferroptosis. Box plots and violine plots were created and verified to confirm the significance of identified target genes. Moreover, ROC monofactor analysis was performed to determine the diagnostic value of identified genes. Two genes (ASNS, SESN2) were subsequently obtained. For the tow genes, STRING was used to obtain the five related genes and determined enriched GO terms and KEGG pathways for those genes.

Conclusion: Our results suggest that ASNS and SENS2 may serve as potential diagnostic biomarkers for AD and provide additional evidence regarding the essential role of ferroptosis in AD.

Keywords: ASNS; Alzheimer’s disease; SESN2; biomarkers; ferroptosis; hippocampus.