Identification and Validation of Autophagy-related Genes in Kawasaki Disease

Overview

Journal Hereditas

Specialty Genetics

Date 2023 Apr 21

PMID 37085930

Authors

Hao Zhu

Biao Xu

Cunshu Hu

Aimin Li

Qing Liao

Affiliations

Soon will be listed here.

Abstract

Background: Kawasaki disease (KD) is a systemic vasculitis of unknown etiology affecting mainly children. Studies have shown that the pathogenesis of KD may be related to autophagy. Using bioinformatics analysis, we assessed the significance of autophagy-related genes (ARGs) in KD.

Methods: Common ARGs were identified from the GeneCards Database, the Molecular Signatures Database (MSigDB), and the Gene Expression Omnibus (GEO) database. ARGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network analysis. Furthermore, related microRNAs (miRNAs), transcription factors (TFs), and drug interaction network were predicted. The immune cell infiltration of ARGs in tissues was explored. Finally, we used receiver operating characteristic (ROC) curves and quantitative real-time PCR (qRT-PCR) to validate the diagnostic value and expression levels of ARGs in KD.

Results: There were 20 ARGs in total. GO analysis showed that ARGs were mainly rich in autophagy, macro-autophagy, and GTPase activity. KEGG analysis showed that ARGs were mainly rich in autophagy-animal and the collecting duct acid secretion pathway. The expression of WIPI1, WDFY3, ATP6V0E2, RALB, ATP6V1C1, GBA, C9orf72, LRRK2, GNAI3, and PIK3CB is the focus of PPI network. A total of 72 related miRNAs and 130 related TFs were predicted by miRNA and TF targeting network analyses. Ten pairs of gene-drug interaction networks were also predicted; immune infiltration analysis showed that SH3GLB1, ATP6V0E2, PLEKHF1, RALB, KLHL3, and TSPO were closely related to CD8 + T cells and neutrophils. The ROC curve showed that ARGs had good diagnostic value in KD. qRT-PCR showed that WIPI1 and GBA were significantly upregulated.

Conclusion: Twenty potential ARGs were identified by bioinformatics analysis, and WIPI1 and GBA may be used as potential drug targets and biomarkers.

Citing Articles

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Cai L, Tang S, Liu Y, Zhang Y, Yang Q Front Mol Neurosci. 2023; 16:1274268.

PMID: 37908486 PMC: 10614158. DOI: 10.3389/fnmol.2023.1274268.

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