Division of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Guangdong Key Laboratory of Urology, Division of Urology Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Medicine (Baltimore). 2024 Jul 26;103(30):e33705. doi: 10.1097/MD.0000000000033705.
Chronic kidney disease (CKD) inevitably progresses to end-stage renal disease if intervention does not occur timely. However, there are limitations in predicting the progression of CKD by solely relying on changes in renal function. A biomarker with high sensitivity and specificity that can predict CKD progression early is required. We used the online Gene Expression Omnibus microarray dataset GSE45980 to identify differentially expressed genes (DEGs) in patients with progressive and stable CKD. We then performed functional enrichment and protein-protein interaction network analysis on DEGs and identified key genes. Finally, the expression patterns of key genes were verified using the GSE60860 dataset, and the receiver operating characteristic curve analysis was performed to clarify their predictive ability of progressive CKD. Ultimately, we verified the expression profiles of these hub genes in an in vitro renal interstitial fibrosis model by real-time PCR and western blot analysis. Differential expression analysis identified 50 upregulated genes and 47 downregulated genes. The results of the functional enrichment analysis revealed that upregulated DEGs were mainly enriched in immune response, inflammatory response, and NF-κB signaling pathways, whereas downregulated DEGs were mainly related to angiogenesis and the extracellular environment. Protein-protein interaction network and key gene analysis identified CCR7 as the most important gene. CCR7 mainly plays a role in immune response, and its only receptors, CCL19 and CCL21, have also been identified as DEGs. The receiver operating characteristic curve analysis of CCR7, CCL19, and CCL21 found that CCR7 and CCL19 present good disease prediction ability. CCR7 may be a stable biomarker for predicting CKD progression, and the CCR7-CCL19/CCL21 axis may be a therapeutic target for end-stage renal disease. However, further experiments are needed to explore the relationship between these genes and CKD.
慢性肾脏病（CKD）如果不及时干预，必然会进展为终末期肾病。然而，仅依靠肾功能的变化来预测 CKD 的进展存在局限性。需要一种具有高灵敏度和特异性的生物标志物，以便能够早期预测 CKD 的进展。
我们使用在线基因表达综合数据集 GSE45980 来鉴定进展性和稳定性 CKD 患者中的差异表达基因（DEGs）。然后，我们对 DEGs 进行功能富集和蛋白质-蛋白质相互作用网络分析，并鉴定关键基因。最后，使用 GSE60860 数据集验证关键基因的表达模式，并进行受试者工作特征曲线分析，以明确它们对进展性 CKD 的预测能力。最终，我们通过实时 PCR 和 Western blot 分析在体外肾间质纤维化模型中验证了这些枢纽基因的表达谱。
差异表达分析鉴定出 50 个上调基因和 47 个下调基因。功能富集分析的结果表明，上调的 DEGs 主要富集在免疫反应、炎症反应和 NF-κB 信号通路中，而下调的 DEGs 主要与血管生成和细胞外环境有关。蛋白质-蛋白质相互作用网络和关键基因分析确定 CCR7 为最重要的基因。CCR7 主要在免疫反应中发挥作用，其唯一的受体 CCL19 和 CCL21 也被鉴定为 DEGs。CCR7、CCL19 和 CCL21 的受试者工作特征曲线分析发现 CCR7 和 CCL19 具有良好的疾病预测能力。CCR7 可能是预测 CKD 进展的稳定生物标志物，CCR7-CCL19/CCL21 轴可能是终末期肾病的治疗靶点。然而，需要进一步的实验来探索这些基因与 CKD 之间的关系。
