Bai Fang, Wang Chunjie, Fan Xin, Fang Lin, Li Luyao, Zhang Xiaoning, Yu Kuipeng, Liu Lei, Guo Ling, Yang Xiangdong
Department of Nephrology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
Laboratory of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.
Heliyon. 2024 Mar 12;10(6):e27754. doi: 10.1016/j.heliyon.2024.e27754. eCollection 2024 Mar 30.
The incidence of chronic kidney disease (CKD) has been increasing in recent years, gradually becoming a global health crisis. Due to limited treatment options, novel molecular pathways are urgently required to advance the treatment and diagnosis of CKD.
The characteristics of differentially expressed genes (DEGs) in CKD patients were analyzed using Gene Expression Omnibus (GEO) database, and genes related to oxidative stress were retrieved from the Genecard database. Subsequently, a comprehensive approach was applied, including immune infiltration analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis, to identify hub genes among differentially expressed immune-related oxidative stress genes (DEIOSGs). Validation of hub genes was performed using an external data set, and diagnostic potential capability was evaluated through receiver operating curve (ROC) analysis. In animal experiments, the expression of hub genes in CKD was confirmed by inducing a CKD model through a 5/6 nephrectomy procedure. Finally, the relationship between these hub genes and clinical characteristics were assessed using the Nephroseq v5 database.
29 DEIOSGs were identified by comprehensive bioinformatics analysis. PPI analysis screened the hub genes NCF2, S100A9, and SELL. ROC analysis demonstrated excellent diagnostic efficacy. Further validation from other databases and animal experiments confirmed a substantial upregulation in the expression of hub genes in CKD. Additionally, clinical correlation analysis established a clear link between hub gene expression and renal function deterioration.
Our study confirms NCF2, S100A9, and SELL as diagnostic biomarkers associated with immune response and oxidative stress in CKD, suggesting their potential as novel targets for CKD diagnosis and treatment.
近年来，慢性肾脏病（CKD）的发病率不断上升，逐渐成为全球健康危机。由于治疗选择有限，迫切需要新的分子途径来推进CKD的治疗和诊断。
利用基因表达综合数据库（GEO）分析CKD患者中差异表达基因（DEG）的特征，并从基因卡片数据库中检索与氧化应激相关的基因。随后，采用综合方法，包括免疫浸润分析、加权基因共表达网络分析（WGCNA）和蛋白质-蛋白质相互作用（PPI）网络分析，以识别差异表达的免疫相关氧化应激基因（DEIOSG）中的枢纽基因。使用外部数据集对枢纽基因进行验证，并通过受试者工作特征曲线（ROC）分析评估诊断潜力。在动物实验中，通过5/6肾切除手术诱导CKD模型，证实了枢纽基因在CKD中的表达。最后，使用Nephroseq v5数据库评估这些枢纽基因与临床特征之间的关系。
通过综合生物信息学分析鉴定出29个DEIOSG。PPI分析筛选出枢纽基因NCF2、S100A9和SELL。ROC分析显示出优异的诊断效能。来自其他数据库和动物实验的进一步验证证实了CKD中枢纽基因表达的显著上调。此外，临床相关性分析建立了枢纽基因表达与肾功能恶化之间的明确联系。
我们的研究证实NCF2、S100A9和SELL是与CKD免疫反应和氧化应激相关的诊断生物标志物，表明它们作为CKD诊断和治疗新靶点的潜力。
