Copper metabolism-related biomarkers and therapeutic targets for diabetic nephropathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41438111", "kind": "science-record", "revision": 4, "content_hash": "sha256:f6763292a8ee141ebc2ba63f1f1d28cea9ff38d3257398dd8ad5da751a9fc449", "created_at": "2026-11-01T20:31:25Z", "updated_at": "2026-11-01T22:57:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Copper metabolism-related biomarkers and therapeutic targets for diabetic nephropathy.", "doi": "10.7717/peerj.20468", "pmid": "41438111", "authors": ["Qiaofang Yan", "Yuanyuan Du", "Fei Huang", "Min Zhan", "Qifan Zheng", "Qiaoxuan Zhang", "Pengwei Zhang", "Jun Yan", "Xiaobin Wu", "Haibiao Lin", "Xianzhang Huang", "Liqiao Han"], "journal": "PeerJ", "year": 2025, "abstract": "Background: Diabetic nephropathy (DN) is the most intractable complication of diabetes. Despite decades of research, accurate diagnostic markers and effective therapeutic drugs are still elusive. Abnormal copper metabolism is also implicated in diabetes and its complications. This study aims to identify copper metabolism-related biomarkers and potential drugs for DN.\nMethods: DN datasets and copper metabolism-related genes (CMGs) were obtained from Gene Expression Omnibus (GEO) and GeneCards. Differentially expressed CMGs (DE-CMGs) were identified using the limma package and the Venn algorithm. Functional enrichment analysis and protein-protein interaction (PPI) network were performed to identify candidate hub genes. The single gene with an area under the receiver operating characteristic (ROC) curve > 0.7 was identified as a potential diagnostic biomarker of DN. Finally, these biomarkers were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in high-glucose-treated human proximal tubular (HK-2) cells. These validated hub genes were used to construct a combined prediction model, confirmed by additional GSE30528 and GSE30529 datasets. The correlation analysis between the expression level of the hub genes and the estimated glomerular filtration rate (eGFR) was carried out. Additionally, immune cell infiltration and potential target drugs were investigated for these biomarkers.\nResults: Five hub genes associated with copper metabolism, namely CD36, CCL2, CASP3, LPL, and APOC3, were identified as biomarkers for the early diagnosis of DN. Utilizing multiple biomarkers enhanced diagnostic accuracy and specificity. CD36, CCL2, and CASP3 correlated negatively with eGFR levels, while LPL and APOC3 correlated positively. Additionally, these hub genes were significantly linked to various immune cell types, including macrophages M1 and M2, T cells, gamma delta resting dendritic cells, neutrophils, and NK cells. Furthermore, 15 agents targeting these biomarkers were retrieved from the DrugBank database.\nConclusion: Our study identified key genes possibly related to copper metabolism in the pathological mechanism of DN that could serve as novel targets for the diagnosis and therapy of DN.", "claims": [{"id": "claim-method", "statement": "Following the predetermined statistical threshold of —log2 Fold Change —>0.5 and P-values < 0.05, DEGs were identified utilizing the limma package in R software (version 4.3.1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41438111", "locator": "sections[5] \"Identification of DE-CMGs in DN\" paragraph 2", "quote": "Following the predetermined statistical threshold of —log2 Fold Change —>0.5 and P-values < 0.05, DEGs were identified utilizing the limma package in R software (version 4.3.1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data are available in the Supplemental Files.The dataset is available at GeneCards: https://www.genecards.org/ - The dataset is hosted in a restricted-access repository. To download it, users must register for a free account on the platform. Users must search “copper metabolism” after logging in.The dataset is available at Nephroseq v5: https://www.nephroseq.org/ - The dataset is hosted in a restricted-access repository. To download it, users must register for a free account on the platform using academic credentials. Key genes: CD36, CASP3, LPL, APOC3, and CCL2", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41438111", "locator": "sections[28] \"Additional Information and Declarations\" paragraph 5", "quote": "The raw data are available in the Supplemental Files.The dataset is available at GeneCards: https://www.genecards.org/ - The dataset is hosted in a restricted-access repository. To download it, users must register for a free account on the platform. Users must search “copper metabolism” after logging in.The dataset is available at Nephroseq v5: https://www.nephroseq.org/ - The dataset is hosted in a restricted-access repository. To download it, users must register for a free account on the platform using academic credentials. Key genes: CD36, CASP3, LPL, APOC3, and CCL2"}], "state": "complete"}, {"id": "claim-target-result", "statement": "Five hub genes associated with copper metabolism, namely CD36, CCL2, CASP3, LPL, and APOC3, were identified as biomarkers for the early diagnosis of DN.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41438111", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Five hub genes associated with copper metabolism, namely CD36, CCL2, CASP3, LPL, and APOC3, were identified as biomarkers for the early diagnosis of DN."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Five hub genes associated with copper metabolism, namely CD36, CCL2, CASP3, LPL, and APOC3, were identified as biomarkers for the early diagnosis of DN.", "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:41438111"], "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:GSE30122"], "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:GSE30122"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41438111", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.20468", "sha256": "sha256:8ce6bd08917418abe5862465a409dc6aeec36b8b0a1bc9a99bcf390f074df885", "bytes": 34981, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.20468", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12721120", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE30122", "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=GSE30122", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE30122", "version": null, "note": "The raw data are available in the Supplemental Files.The dataset is available at GeneCards: https://www.genecards.org/ - The dataset is hosted in a restricted-access repository. To download it, users must register for a free account on the platform. Users must search “copper metabolism” after logging in.The dataset is available at Nephroseq v5: https://www.nephroseq.org/ - The dataset is hosted in a restricted-access repository. To download it, users must register for a free account on the platform using academic credentials. Key genes: CD36, CASP3, LPL, APOC3, and CCL2", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data are available in the Supplemental Files.The dataset is available at GeneCards: https://www.genecards.org/ - The dataset is hosted in a restricted-access repository. To download it, users must register for a free account on the platform. Users must search “copper metabolism” after logging in.The dataset is available at Nephroseq v5: https://www.nephroseq.org/ - The dataset is hosted in a restricted-access repository. 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To download it, users must register for a free account on the platform. Users must search “copper metabolism” after logging in.The dataset is available at Nephroseq v5: https://www.nephroseq.org/ - The dataset is hosted in a restricted-access repository. To download it, users must register for a free account on the platform using academic credentials. Key genes: CD36, CASP3, LPL, APOC3, and CCL2", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data are available in the Supplemental Files.The dataset is available at GeneCards: https://www.genecards.org/ - The dataset is hosted in a restricted-access repository. To download it, users must register for a free account on the platform. Users must search “copper metabolism” after logging in.The dataset is available at Nephroseq v5: https://www.nephroseq.org/ - The dataset is hosted in a restricted-access repository. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:41438111", "data:geo:GSE30122"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE30122"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:08:52Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9714, "completion_tokens": 2233, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:41438111", "type": "paper", "label": "pmid:41438111"}, {"id": "source:pmid:41438111", "type": "manuscript", "label": "PMID 41438111 full text"}, {"id": "data:geo:GSE30122", "type": "dataset", "label": "GEO GSE30122"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41438111", "type": "paper", "label": "pmid:41438111"}, {"id": "source:pmid:41438111", "type": "manuscript", "label": "PMID 41438111 full text"}, {"id": "data:geo:GSE30122", "type": "dataset", "label": "GEO GSE30122"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41438111", "type": "extraction", "used": ["source:pmid:41438111"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE30122", "type": "accession_resolution", "used": ["data:geo:GSE30122"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:41438111", "parent_hash": "sha256:3d12f6863143d00953f79eda780bbbfce4dacb961b1d91328ca39fffea0b762f", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE30122 licence not read", "asset:data:geo:GSE30122 not downloaded", "asset:data:geo:GSE30528 licence not read", "asset:data:geo:GSE30528 not downloaded", "asset:data:geo:GSE30529 licence not read", "asset:data:geo:GSE30529 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["notype and experimental stability. 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