ECHS1 expression level of patients.

Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome and often leads to end-stage renal disease. However, the underlying pathophysiological mechanisms that contribute to disease progression require further investigation to establish appropriate therapeutic targets and biomarkers. This study aimed to clarify the molecular mechanisms underlying FSGS by focusing on differentially expressed genes (DEGs) and lipid metabolism-related genes (LMRGs). We utilized the GSE69814, GSE129973, and GSE121233 datasets, which comprise glomerular transcriptomes from patients with FSGS, minimal change disease (MCD), and unaffected kidney tissues. We identified 2,459 DEGs from the GSE69814 dataset and 982 DEGs from the GSE129973 dataset. These DEGs intersected 1,450 LMRGs, resulting in 56 differentially expressed LMRGs (DELMRGs). Enrichment analysis revealed that these DELMRGs were primarily involved in fatty acid metabolic processes; localized in microbodies, peroxisomes, and mitochondrial matrices; and exhibited oxidoreductase activity. Protein-protein interaction networks were constructed using Cytoscape, and five hub DELMRGs (enoyl-CoA hydratase, short chain 1 [ECHS1], EHHADH, IDH1, SUCLG1, and ALDH3A2) were identified using multiple algorithms. We assessed the diagnostic performance using receiver operating characteristic curves and expression levels from the GSE121233 dataset, and found that ECHS1 and ALDH3A2 showed strong diagnostic potential. Immunohistochemical verification of clinical specimens from children confirmed significant expression of ECHS1 in FSGS compared with that in normal and MCD tissues. This study highlights ECHS1 as a potential biomarker for pediatric FSGS, suggesting a potential role in early diagnosis or personalized treatment, offering insights into its pathogenesis and paving the way for targeted therapeutic strategies.

局灶节段性肾小球硬化（Focal segmental glomerulosclerosis, FSGS）是肾病综合征的常见病因，常可进展为终末期肾病。然而，介导疾病进展的潜在病理生理机制仍有待进一步研究，以确立合适的治疗靶点与生物标志物。本研究聚焦于差异表达基因（differentially expressed genes, DEGs）与脂质代谢相关基因（lipid metabolism-related genes, LMRGs），旨在阐明FSGS的分子机制。我们采用了GSE69814、GSE129973与GSE121233数据集，上述数据集涵盖了FSGS患者、微小病变肾病（minimal change disease, MCD）患者及正常肾组织的肾小球转录组数据。从GSE69814数据集中共鉴定出2459个差异表达基因，从GSE129973数据集中共鉴定出982个差异表达基因。将上述差异表达基因与1450个脂质代谢相关基因进行交集分析，得到56个差异表达脂质代谢相关基因（differentially expressed LMRGs, DELMRGs）。富集分析结果显示，这些差异表达脂质代谢相关基因主要参与脂肪酸代谢过程，定位于微体、过氧化物酶体及线粒体基质，并具有氧化还原酶活性。使用Cytoscape构建蛋白质相互作用网络，并通过多种算法筛选出5个核心差异表达脂质代谢相关基因：烯酰辅酶A水合酶短链1（enoyl-CoA hydratase, short chain 1, ECHS1）、EHHADH、IDH1、SUCLG1及ALDH3A2。我们采用受试者工作特征曲线（receiver operating characteristic, ROC）结合GSE121233数据集的表达水平评估诊断效能，发现ECHS1与ALDH3A2展现出较强的诊断潜力。对儿童临床标本的免疫组化验证结果证实，相较于正常组织与MCD组织，FSGS组织中ECHS1的表达水平显著升高。本研究表明ECHS1可作为儿童FSGS的潜在生物标志物，可为其早期诊断或个性化治疗提供新思路，同时为阐明FSGS的发病机制及开发靶向治疗策略奠定基础。