{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:12:54Z","timestamp":1792872774712,"version":"4.5.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016039","name":"Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center","doi-asserted-by":"publisher","award":["Gui Ke AD22035219"],"award-info":[{"award-number":["Gui Ke AD22035219"]}],"id":[{"id":"10.13039\/100016039","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Research Project of Guangxi Zhuang Autonomous Region Health Commissiont","award":["Z20240552"],"award-info":[{"award-number":["Z20240552"]}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2023JJ30550"],"award-info":[{"award-number":["2023JJ30550"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>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 [<jats:italic>ECHS1<\/jats:italic>]<jats:italic>, EHHADH, IDH1, SUCLG1<\/jats:italic>, and <jats:italic>ALDH3A2<\/jats:italic>) 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 <jats:italic>ECHS1<\/jats:italic> and <jats:italic>ALDH3A2<\/jats:italic> showed strong diagnostic potential. Immunohistochemical verification of clinical specimens from children confirmed significant expression of <jats:italic>ECHS1<\/jats:italic> in FSGS compared with that in normal and MCD tissues. This study highlights <jats:italic>ECHS1<\/jats:italic> 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.<\/jats:p>","DOI":"10.1371\/journal.pone.0319049","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T20:07:08Z","timestamp":1741637228000},"page":"e0319049","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["ECHS1 as a Lipid Metabolism Biomarker for Pediatric Focal Segmental 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