Liu Lichun, Lai Yongxing, Zhan Zhidong, Fu Qingxian, Jiang Yuelian
Department of Pharmacy, Fujian Children's Hospital, Fuzhou, China.
Department of Geriatric Medicine, Fujian Provincial Hospital, Fuzhou, China.
Front Neurol. 2022 Feb 14;12:816393. doi: 10.3389/fneur.2021.816393. eCollection 2021.
Friedreich's ataxia (FRDA) is a familial hereditary disorder that lacks available therapy. Therefore, the identification of novel biomarkers and key mechanisms related to FRDA progression is urgently required.
We 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. We identified 88 co-DEGs between child and adult FRDA samples. 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. We verified eight immune-specific core genes 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.
弗里德赖希共济失调（FRDA）是一种缺乏有效治疗方法的家族遗传性疾病。因此，迫切需要鉴定与FRDA进展相关的新型生物标志物和关键机制。
我们从GSE11204数据集中鉴定出儿童和成人FRDA中上调和下调的差异表达基因（DEG），并将它们进行交集分析以确定共表达的DEG（co-DEG）。进行富集分析并构建蛋白质-蛋白质相互作用（PPI）网络以识别关键途径和枢纽基因。使用GSE30933数据集验证潜在的诊断生物标志物。应用Cytoscape构建相互作用和竞争性内源RNA（ceRNA）网络。
基因集富集分析（GSEA）表明，儿童和成人样本中的基因主要富集于其免疫相关功能。我们在儿童和成人FRDA样本之间鉴定出88个共表达DEG。基因本体论（GO）、京都基因与基因组百科全书（KEGG）和Reactome富集分析表明，这些共表达DEG主要富集于免疫反应、炎症反应和坏死性凋亡。免疫浸润分析显示，FRDA与健康样本之间免疫细胞亚型比例存在显著差异。此外，基于PPI网络筛选出10个核心基因和1个基因簇模块。我们使用验证数据集验证了8个免疫特异性核心基因，发现CD28、FAS和ITIF5在FRDA中具有较高的诊断意义。最后，NEAT1-hsa-miR-24-3p-CD28被确定为儿童和成人FRDA的关键调控途径。
三种免疫特异性枢纽基因CD28、FAS和IFIT5的下调可能与儿童和成人FRDA的进展有关。此外，NEAT1-hsa-miR-24-3p-CD28可能是与儿童和成人FRDA发病机制相关的潜在RNA调控途径。
