Integrated bioinformatics and clinical validation reveals PRDX6 as a mitochondrial hub gene in systemic lupus erythematosus.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41495309", "kind": "science-record", "revision": 3, "content_hash": "sha256:2b47d79f3f846815a74fe0cf4cbdb3f72db9387ce73fff96b23d536b3e23352c", "created_at": "2026-11-01T20:31:28Z", "updated_at": "2026-11-01T22:15:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated bioinformatics and clinical validation reveals PRDX6 as a mitochondrial hub gene in systemic lupus erythematosus.", "doi": "10.1007/s10067-025-07860-8", "pmid": "41495309", "authors": ["Xingyu Liu", "Yan Xiao", "Yaxin Deng", "Jie Chen", "Ting Peng", "Yixin Jin", "Qian Dai", "Mei Zeng"], "journal": "Clinical rheumatology", "year": 2026, "abstract": "OBJECTIVES: Peroxiredoxin 6 (PRDX6), a potent antioxidant enzyme, has garnered considerable interest for its potential involvement in inflammatory diseases. However, the relationship between PRDX6 and SLE remains poorly understood. This study aims to elucidate the association between PRDX6 and SLE, providing insights into its potential role in disease mechanisms.\nMETHOD: Gene expression datasets (GSE50772, GSE61635) from the GEO database were merged and batch-corrected (sva, limma). DEGs were identified and SLE-associated gene modules were analyzed by weighted gene co-expression network analysis (WGCNA). Intersecting differentially expressed genes (DEGs), module genes, and MitoCarta3.0-defined mitochondria-associated DEGs, which were refined by LASSO, Random Forest, and SVM-RFE to select hub genes. The expression levels of PRDX6 in peripheral blood mononuclear cells (PBMCs) from SLE patients were measured by quantitative PCR and Western blot analysis.\nRESULTS: A total of 1581 DEGs (865 upregulated, 716 downregulated) were identified. WGCNA revealed a key module of 1615 genes; intersecting this module with DEGs and MitoCarta3.0 yielded 36 mitochondria-associated DEGs. Three machine learning methods narrowed these to 11 core genes, including PRDX6. The expression levels of PRDX6 were significantly lower in SLE PBMCs than in healthy controls, especially in active SLE. Patients with renal or joint involvement had lower PRDX6 levels. The mRNA levels of PRDX6 showed an inverse correlation with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score.\nCONCLUSIONS: This study suggested that PRDX6 might be a potential biomarker and exert protective effects by reducing oxidative stress in SLE. Key Points • IFI27 and PRDX6 serve as potential mitochondrial-related biomarkers in SLE. • PRDX6 is significantly downregulated in SLE. • PRDX6 is associated with SLEDAI score.", "claims": [{"id": "claim-method", "statement": "Spearman’s rank correlation analysis was performed to evaluate (i) the association between PRDX6 mRNA levels in PBMCs from SLE patients and disease activity (SLEDAI score), (ii) systemic inflammatory markers (ESR, CRP), (iii) immunological parameters (anti-dsDNA antibody titers, complement C3/C4 levels), and (iv) organ-specific involvement (renal, articular, mucocutaneous, and hematologic manifestations).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41495309", "locator": "sections[9] \"Correlation of PRDX6 mRNA levels with clinical parameters\" paragraph 2", "quote": "Spearman’s rank correlation analysis was performed to evaluate (i) the association between PRDX6 mRNA levels in PBMCs from SLE patients and disease activity (SLEDAI score), (ii) systemic inflammatory markers (ESR, CRP), (iii) immunological parameters (anti-dsDNA antibody titers, complement C3/C4 levels), and (iv) organ-specific involvement (renal, articular, mucocutaneous, and hematologic manifestations)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All gene expression data used in this study are publicly available from the Gene Expression Omnibus (GEO) under accession numbers GSE50772 and GSE61635 (https://www.ncbi.nlm.nih.gov/geo/). The mitochondrial gene list was retrieved from the Mitocarta3.0 database (https://www.broadinstitute.org/mitocarta).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41495309", "locator": "sections[27] \"Data availability\" paragraph 2", "quote": "All gene expression data used in this study are publicly available from the Gene Expression Omnibus (GEO) under accession numbers GSE50772 and GSE61635 (https://www.ncbi.nlm.nih.gov/geo/). The mitochondrial gene list was retrieved from the Mitocarta3.0 database (https://www.broadinstitute.org/mitocarta)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "PRDX6 mRNA expression in SLE patient PBMCs was negatively correlated with SLEDAI scores.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "PRDX6 mRNA expression in SLE patient PBMCs was negatively correlated with SLEDAI scores (r = − 0.502, P < 0.001) (Table 3)."}, "evidence": [{"asset": "source:pmid:41495309", "locator": "sections[20] \"The PRDX6 mRNA levels correlate with specific clinical manifestations in SLE\" paragraph 2", "quote": "PRDX6 mRNA expression in SLE patient PBMCs was negatively correlated with SLEDAI scores (r = − 0.502, P < 0.001) (Table 3)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "PRDX6 mRNA expression in SLE patient PBMCs was negatively correlated with SLEDAI scores.", "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:41495309"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE50772"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE50772"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41495309", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s10067-025-07860-8", "sha256": "sha256:e534217f79e35b45252224f974e41717402bb34b4adee81ba73a611d7fc3d063", "bytes": 42586, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s10067-025-07860-8", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12858600", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE50772", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50772", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE50772", "version": null, "note": "All gene expression data used in this study are publicly available from the Gene Expression Omnibus (GEO) under accession numbers GSE50772 and GSE61635 (https://www.ncbi.nlm.nih.gov/geo/). The mitochondrial gene list was retrieved from the Mitocarta3.0 database (https://www.broadinstitute.org/mitocarta).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All gene expression data used in this study are publicly available from the Gene Expression Omnibus (GEO) under accession numbers GSE50772 and GSE61635 (https://www.ncbi.nlm.nih.gov/geo/). 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A run that reproduces the effect is judged against this threshold."}], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE50772", "GSE61635", "GSE72509"], "resolved_accessions": ["GSE50772", "GSE61635", "GSE72509"], "statements": ["All gene expression data used in this study are publicly available from the Gene Expression Omnibus (GEO) under accession numbers GSE50772 and GSE61635 (https://www.ncbi.nlm.nih.gov/geo/). The mitochondrial gene list was retrieved from the Mitocarta3.0 database (https://www.broadinstitute.org/mitocarta)."], "basis": "The paper names GSE50772, GSE61635, GSE72509 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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