Decoding Cuproptosis-Sphingolipid-Immune Crosstalk in Atopic Dermatitis: A Multi-Omics Network Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40564068", "kind": "science-record", "revision": 3, "content_hash": "sha256:7adf2f719cd98aa9ad927d8ee80398904e4f1c4fb4bfe1de807158cce1496bac", "created_at": "2026-11-01T20:30:39Z", "updated_at": "2026-11-01T22:14:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Decoding Cuproptosis-Sphingolipid-Immune Crosstalk in Atopic Dermatitis: A Multi-Omics Network Analysis.", "doi": "10.3390/biomedicines13061349", "pmid": "40564068", "authors": ["Xiaowen Wen", "Shulin Jia", "Jing Wu", "Suitian Wang", "Teng Yu", "Haoyou Xu"], "journal": "Biomedicines", "year": 2025, "abstract": "Background: This study pioneers the exploration of the role of cuproptosis (a novel form of regulated cell death) in the pathogenesis of atopic dermatitis (AD). Methods: We integrated two datasets (GSE157194 and GSE193309) from the GEO database and employed weighted gene co-expression network analysis (WGCNA) to identify disease-related modules. Through multi-dimensional approaches, including differential gene expression analysis, functional enrichment analysis, GeneMANIA network construction, GSEA/GSVA pathway enrichment analysis, and immune infiltration analysis, we systematically elucidated the regulatory mechanisms of cuproptosis-related genes (CRGs) in AD. Results: The findings reveal novel mechanisms underlying AD pathogenesis. We identified 14 co-expression modules and 1173 differentially expressed genes, among which SPTLC2, AMD1, and IGSF3 were identified as key hub genes (AUC > 0.75). In-depth mechanistic analysis uncovered critical pathophysiological features of AD, including significant enrichment in chemokine signaling pathways (p < 0.001) and copper-dependent metabolic reprogramming. Notably, immune infiltration analysis demonstrated abnormal activity in 20 out of 21 immune cell types, particularly Th2 cells and macrophages, which showed strong correlations with CRG expression patterns. These findings establish an innovative \"metabolic checkpoint\" model for AD progression, highlighting dysregulation of the sphingolipid-immune axis as a key pathogenic mechanism. Conclusions: This study provides novel evidence, suggesting a potential link between AD and copper metabolism dysregulation, and identifies several promising targets that may aid in diagnosis and treatment. Our findings contribute to the growing understanding of AD pathogenesis and hint at possible new therapeutic directions, including copper chelation or sphingolipid-modulating approaches for difficult-to-treat AD cases. The identified CRG signatures may serve as potential biomarkers and therapeutic targets for personalized management strategies of this complex skin disorder.", "claims": [{"id": "claim-method", "statement": "This was accomplished through the application of the WGCNA (version 1.70-3) package within the R programming environment [32].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40564068", "locator": "sections[6] \"2.4. WGCNA Analysis and Identification of Significant Modules\" paragraph 2", "quote": "This was accomplished through the application of the WGCNA (version 1.70-3) package within the R programming environment [32]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40564068", "locator": "sections[31] \"notes\" paragraph 1", "quote": "All data generated or analyzed during this study are included in this published article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "WGCNA identified 14 co-expression modules, with the greenyellow module showing the strongest association with cuproptosis induction (Pearson’s r = 0.6541, p < 0.05).", "kind": "quantitative", "target": {"value": 0.6541, "unit": "correlation coefficient", "tolerance": null, "source": "Comprehensive correlation analyses of 14 module eigengenes revealed that the greenyellow module (n = 117, Table S1) had the strongest association with cuproptosis induction (Pearson’s r = 0.6541, p < 0.05), highlighting its role in copper-dependent cell death regulation for further study (Figure 2D)."}, "evidence": [{"asset": "source:pmid:40564068", "locator": "sections[14] \"3.1. Identification of Key WGCNA Module and DEGs\" paragraph 2", "quote": "This resulted in the identification of 14 co-expression modules, without unrelated genes in the gray module (Figure 2B)."}, {"asset": "source:pmid:40564068", "locator": "sections[14] \"3.1. Identification of Key WGCNA Module and DEGs\" paragraph 2", "quote": "Comprehensive correlation analyses of 14 module eigengenes revealed that the greenyellow module (n = 117, Table S1) had the strongest association with cuproptosis induction (Pearson’s r = 0.6541, p < 0.05), highlighting its role in copper-dependent cell death regulation for further study (Figure 2D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "WGCNA identified 14 co-expression modules, with the greenyellow module showing the strongest association with cuproptosis induction (Pearson’s r = 0.6541, p < 0.05).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40564068"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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