Screening potential diagnostic biomarkers for PLA2R‑associated idiopathic membranous nephropathy by WGCNA analysis and LASSO algorithm.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39806779", "kind": "science-record", "revision": 4, "content_hash": "sha256:284898e367d0d5640677c744f58bc59fc3b33bf30f50666b149b09be316e8863", "created_at": "2026-11-01T20:30:07Z", "updated_at": "2026-11-01T22:56:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Screening potential diagnostic biomarkers for PLA2R‑associated idiopathic membranous nephropathy by WGCNA analysis and LASSO algorithm.", "doi": "10.1080/0886022X.2024.2438859", "pmid": "39806779", "authors": ["Jinxu Huang", "Yaqing Huang", "Xiaoling Zeng", "Yuhong Zhang", "Junneng Zhang", "Qingchu Hong", "Yongtiao Peng"], "journal": "Renal failure", "year": 2025, "abstract": "Adult nephrotic syndrome is primarily caused by membranous nephropathy (MN), with idiopathic membranous nephropathy (IMN) being a prominent subtype. The onset of phospholipase A2 receptor (PLA2R1)-associated IMN is critically linked to M-type PLA2R1 exposure, yet the mechanism underlying glomerular injury remains unclear. In this study, membranous nephropathy datasets (GSE115857, GSE200828) were retrieved from GEO. Differential gene expression was analyzed using the 'limma' R package. WGCNA filtered PLA2R-related modules and intersected genes. LASSO regression, evaluated by ROC analysis, identified characteristic genes. Binomial logistic regression assessed their association with IMN. Validation was performed in the GSE133288 dataset. IHC and qRT-PCR detected characteristic gene expression in PLA2R-positive patients. This study identified elevated PLA2R expression in IMN patients among 117 DEGs. PPI analysis suggested enrichment in Golgi membranes, co-regulation, and glucocorticoid responsiveness, implicating the PPAR pathway by KEGG. WGCNA revealed a 440-gene brown module associated with IMN-PLA2R, with ECM1, SLC19A2, RASD1, FOSB, KDELR3, ZFP36, and ELF4 highlighted as diagnostic markers by ROC analysis. Clinical validation confirmed ECM1 upregulation increased IMN risk, while upregulation of SLC19A2, ZFP36, RASD1, and FOSB decreased it. ECM1 positively correlated with PLA2R, whereas SLC19A2, ZFP36, and FOSB negatively correlated. IHC analysis demonstrated consistent gene expression patterns in IMN tissues, with podocyte exposure to PLA2R-positive serum reducing viability and increasing apoptosis. Functional studies, prompted by RASD1 downregulation, revealed enhanced cell activity and reduced apoptosis upon RASD1 overexpression compared to the Serum + Ov-NC control. Collectively, this study identified diagnostic markers for PLA2R-related IMN, offering novel therapeutic targets for the treatment of IMN.", "claims": [{"id": "claim-method", "statement": "Utilizing weighted correlation network analysis (WGCNA), modules and genes strongly correlated with PLA2R membranous nephropathy were identified, intersected with the differential genes. Subsequently, LASSO regression refined the characteristic genes, and ROC analysis assessed their sensitivity and specificity. Then, the binomial logistic regression method of the generalized linear model was used to analyze the relationship between the expression of the characteristic genes and IMN.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39806779", "locator": "sections[1] \"Introduction\" paragraph 4", "quote": "Utilizing weighted correlation network analysis (WGCNA), modules and genes strongly correlated with PLA2R membranous nephropathy were identified, intersected with the differential genes. Subsequently, LASSO regression refined the characteristic genes, and ROC analysis assessed their sensitivity and specificity. Then, the binomial logistic regression method of the generalized linear model was used to analyze the relationship between the expression of the characteristic genes and IMN."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The dataset pertaining to MN was retrieved from the GEO database, GSE115857 (IMN = 11, Control = 7) and GSE200828 (IMN = 51, Control = 6) were used as training sets, and GSE133288 (IMN = 48, Control = 5) was used as validation sets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39806779", "locator": "sections[3] \"Data download and processing\" paragraph 2", "quote": "The dataset pertaining to MN was retrieved from the GEO database, GSE115857 (IMN = 11, Control = 7) and GSE200828 (IMN = 51, Control = 6) were used as training sets, and GSE133288 (IMN = 48, Control = 5) was used as validation sets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This study identified diagnostic markers for PLA2R-related IMN, offering novel therapeutic targets for the treatment of IMN.", "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:39806779"], "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:GSE115857"], "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:GSE115857"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39806779", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1080/0886022X.2024.2438859", "sha256": "sha256:8f8ff35192eec3f6113af90a4a4b8cf2936fd6f88eb5e0f4d7fc20c2d5df5dda", "bytes": 38992, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1080/0886022X.2024.2438859", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11734395", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE115857", "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=GSE115857", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE115857", "version": null, "note": "The dataset pertaining to MN was retrieved from the GEO database, GSE115857 (IMN = 11, Control = 7) and GSE200828 (IMN = 51, Control = 6) were used as training sets, and GSE133288 (IMN = 48, Control = 5) was used as validation sets.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The dataset pertaining to MN was retrieved from the GEO database, GSE115857 (IMN = 11, Control = 7) and GSE200828 (IMN = 51, Control = 6) were used as training sets, and GSE133288 (IMN = 48, Control = 5) was used as validation sets.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM3191893", "GSM3191894", "GSM3191895", "GSM3191896", "GSM3191897", "GSM3191898", "GSM3191899", "GSM3191900", "GSM3191901", "GSM3191902", "GSM3191903", "GSM3191904", "GSM3191905", "GSM3191906", "GSM3191907", "GSM3191908", "GSM3191909", "GSM3191910", "GSM3191911", "GSM3191912", "GSM3191913", "GSM3191914", "GSM3191915", "GSM3191916", "GSM3191917", "GSM3191918", "GSM3191919", "GSM3191920", "GSM3191921", "GSM3191922", "GSM3191923", "GSM3191924", "GSM3191925", "GSM3191926", "GSM3191927", "GSM3191928", "GSM3191929", "GSM3191930", "GSM3191931", "GSM3191932", "GSM3191933", "GSM3191934", "GSM3191935", "GSM3191936", "GSM3191937", "GSM3191938", "GSM3191939", "GSM3191940", "GSM3191941", "GSM3191942", "GSM3191943", "GSM3191944", "GSM3191945", "GSM3191946", "GSM3191947", "GSM3191948", "GSM3191949", "GSM3191950", "GSM3191951", "GSM3191952", "GSM3191953", "GSM3191954", "GSM3191955", "GSM3191956", "GSM3191957", "GSM3191958", "GSM3191959", "GSM3191960", "GSM3191961", "GSM3191962", "GSM3191963", "GSM3191964", "GSM3191965", "GSM3191966", "GSM3191967", "GSM3191968", "GSM3191969", "GSM3191970", "GSM3191971", "GSM3191972", "GSM3191973", "GSM3191974", "GSM3191975", "GSM3191976", "GSM3191977", "GSM3191978"], "sample_count": 86, "group_sizes": null, "group_sizes_basis": null, "platform": "14951", "taxon": "Homo sapiens", "title": "SPECIFIC BIOMARKERS ASSOCIATED WITH CHRONIC RENAL LESIONS IN IGA NEPHROPATHY PATIENTS. 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IHC and qRT-PCR detected characteristic gene exp", "19A2, ZFP36, and FOSB negatively correlated. IHC analysis demonstrated consistent gene expres"], "order_basis": "paper_text_order:836", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["tive serum reducing viability and increasing apoptosis. Functional studies, prompted by RASD1 downr", "revealed enhanced cell activity and reduced apoptosis upon RASD1 overexpression compared to the Se"], "order_basis": "paper_text_order:1706", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["als and methods Cell culture, treatment, and transfection Human podocytes (procell, CP-H075, Wuhan, CN", "ium containing 5% FBS but without IFN-γ. For transfection, cells were transfected with RASD1 overexpre", "without IFN-γ. For transfection, cells were transfected with RASD1 overexpression plasmid (Ov-RASD1)", "verexpression plasmid (Ov-RASD1). 48 h after transfection, cells were cultured in medium for further e"], "order_basis": "paper_text_order:2080", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["rocell Life Science Co., Ltd. Podocytes were cultured in culture dishes coated with type I collagen (", "-RASD1). 48 h after transfection, cells were cultured in medium for further experiments. Statistical"], "order_basis": "paper_text_order:2211", "id": "assay:4"}, {"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["glm_logit_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Utilizing weighted correlation network analysis (WGCNA), modules and genes strongly correlated with PLA2R membranous nephropathy were identified, intersected with the differential genes. Subsequently, LASSO regression refined the characteristic genes, and ROC analysis assessed their sensitivity and specificity. Then, the binomial logistic regression method of the generalized linear model was used to analyze the relationship between the expression of the characteristic genes and IMN."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}