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Downregulation of Three Immune-Specific Core Genes and the Regulatory Pathways in Children and Adult Friedreich's Ataxia: A Comprehensive Analysis Based on Microarray

The authors identified the up-regulated and down-regulated differentially expressed genes (DEGs) in children and adult FRDA from the GSE11204 dataset and intersected them to determine the co-expressed DEGs (co-DEGs). Enrichment analysis was conducted and a protein-protein interaction (PPI) network was constructed to identify key pathways and hub genes. The potential diagnostic biomarkers were validated using the GSE30933 dataset. Cytoscape was applied to construct interaction and competitive endogenous RNA (ceRNA) networks. Gene Set Enrichment Analysis (GSEA) indicated that the genes in both the child and adult samples were primarily enriched in their immune-related functions. 88 co-DEGs between child and adult FRDA samples were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment analysis suggested that these co-DEGs were primarily enriched in immune response, inflammatory reaction, and necroptosis. Immune infiltration analysis showed remarkable differences in the proportions of immune cell subtype between FRDA and healthy samples. In addition, ten core genes and one gene cluster module were screened out based on the PPI network. Eight immune-specific core genes weew verified using a validation dataset and found CD28, FAS, and ITIF5 have high diagnostic significance in FRDA. Finally, NEAT1-hsa-miR-24-3p-CD28 was identified as a key regulatory pathway of child and adult FRDA. Downregulation of three immune-specific hub genes, CD28, FAS, and IFIT5, may be associated with the progression of child and adult FRDA. Furthermore, NEAT1-hsa-miR-24-3p-CD28 may be the potential RNA regulatory pathway related to the pathogenesis of child and adult FRDA.

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