Evidence map›Paper›PMID 40789933›Full record

ArticlePediatric research2025

Identification of childhood-onset lupus nephritis through integrative bioinformatics: otoferlin as a novel biomarker.

Xinlei Wu, Xinyue Liang, Yang Li, Siyan Chen, Yuanyuan Xie, Chunyan Hua, Sheng Gao

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Article in Pediatric research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Xinlei Wu *School of the 2nd Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
Xinyue Liang *School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, China.
Yang LiSchool of the 1st Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, China.
Siyan ChenSchool of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, China.
Yuanyuan XieSchool of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
Chunyan HuaSchool of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China. huachunyan@wmu.edu.cn.
Sheng GaoLaboratory Animal Center, Wenzhou Medical University, Wenzhou, China. 4869335@qq.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChildhood-onset systemic lupus erythematosus (cSLE) exhibits a higher incidence of lupus nephritis (LN) compared to adult-onset SLE (aSLE). However, the underlying molecular mechanisms remain elusive.

methodsGene expression datasets from childhood-onset (GSE65391) and adult-onset (GSE72798) LN patients were obtained. Differential gene expression (DEG) and weighted gene co-expression network analysis (WGCNA) identified key modules associated with cLN. Machine learning algorithms (random forest, SVM-RFE) prioritized hub genes, validated by ROC curves. Immune cell profiles analysis (CIBERSORT, ssGSEA, xCell) evaluated immune cell profiles, and functional enrichment (GSEA, GSVA) explored pathway alterations. Molecular docking and drug sensitivity analysis predicted therapeutic targets for  otoferlin (OTOF)-high cLN.

resultsDistinct gene expression profiles were revealed between cLN and aLN, with significant enrichment of interferon (IFN) pathways in cLN. OTOF emerged as a high diagnostic biomarker for cLN, and was positively correlated with activated dendritic cells and associated with the TLR signaling pathway in cLN. Molecular docking predicted strong binding of OTOF to JAK inhibitors, supported by CMap analysis showing sensitivity of OTOF-high cLN to these drugs.

conclusionsIFN-related pathways are crucial for the pathogenesis of cLN. OTOF is a promising blood biomarker and contributes to cLN progression through IFN-related pathways. IMPACT: The molecular mechanisms by which cSLE is more likely to progress to cLN than aSLE are rarely investigated. The crucial role of interferon pathways in cLN pathogenesis is highlighted. OTOF could serve as an early diagnostic biomarker for cLN and promote cLN progression through TLRs. These insights could guide tailored therapeutic strategies for cLN, addressing a critical gap in current clinical management.

Indexed as

Computational BiologyLupus NephritisMembrane ProteinsAdolescentAge of OnsetBiomarkersChildFemaleGene Expression ProfilingGene Regulatory NetworksHumansMachine LearningMolecular Docking SimulationSignal TransductionTranscriptomeBiomarkersMembrane Proteins

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