Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35433866", "kind": "science-record", "revision": 5, "content_hash": "sha256:b4ce6b0142681948176a6bf8d2135cefe7913ae5c298037c7d6c1849e3703bf0", "created_at": "2026-11-01T18:14:16Z", "updated_at": "2026-11-01T22:48:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Subunits of C1Q Are Associated With the Progression of Intermittent Claudication to Chronic Limb-Threatening Ischemia.", "doi": "10.3389/fcvm.2022.864461", "pmid": "35433866", "authors": ["Ziping Yao", "Bihui Zhang", "Guochen Niu", "Ziguang Yan", "Xiaoqiang Tong", "Yinghua Zou", "Min Yang"], "journal": "Frontiers in cardiovascular medicine", "year": 2022, "abstract": "Background: The pathophysiological mechanisms of intermittent claudication (IC) progression to chronic limb-threatening ischemia (CLTI) are still vague and which of patients with IC will become CLTI are unknown. This study aimed to investigate the key molecules and pathways mediating IC progression to CLTI by a quantitative bioinformatic analysis of a public RNA-sequencing database of patients with peripheral artery disease (PAD) to screen biomarkers discriminating IC and CLTI.\nMethods: The GSE120642 dataset was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between IC and CLTI tissues were analyzed using the \"edgeR\" packages of R. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to explore the functions of DEGs. Protein-protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Hub genes were selected by plugin cytoHubba. Gene set enrichment analysis was performed and the receiver operating characteristic curves were used to evaluate the predictive values of hub genes.\nResults: A total of 137 upregulated and 21 downregulated DEGs were identified. Functional enrichment clustering analysis revealed a significant association between DEGs and the complement and coagulation cascade pathways. The PPI network was constructed with 155 nodes and 105 interactions. The most significantly enriched pathway was complement activation. C1QB, C1QA, C1QC, C4A, and C1R were identified and validated as hub genes due to the high degree of connectivity. The area under the curve values for the five hub genes were greater than 0.95, indicating high accuracy for discriminating IC and CLTI.\nConclusion: The complement activation pathway is associated with IC progression to CLTI. C1QB, C1QA, C1QC, C4A, and C1R might serve as potential early biomarkers of CLTI.", "claims": [{"id": "claim-method", "statement": "The R package edgeR was utilized to find differentially expressed genes (DEGs) (11).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35433866", "locator": "sections[4] \"Differentially Expressed Genes Identified by EdgeR\" paragraph 2", "quote": "The R package edgeR was utilized to find differentially expressed genes (DEGs) (11)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35433866", "locator": "sections[18] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The area under the curve values for the five hub genes were greater than 0.95, indicating high accuracy for discriminating IC and CLTI.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35433866", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The area under the curve values for the five hub genes were greater than 0.95, indicating high accuracy for discriminating IC and CLTI."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The area under the curve values for the five hub genes were greater than 0.95, indicating high accuracy for discriminating IC and CLTI.", "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:35433866"], "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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