Exploration of Key Immune-Related Transcriptomes Associated with Doxorubicin-Induced Cardiotoxicity in Patients with Breast Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37684436", "kind": "science-record", "revision": 5, "content_hash": "sha256:a9b0112291b015e60e9c16862525204e267fe08f835ebee441b64a1ba1c283c2", "created_at": "2026-11-01T19:02:29Z", "updated_at": "2026-11-01T22:52:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploration of Key Immune-Related Transcriptomes Associated with Doxorubicin-Induced Cardiotoxicity in Patients with Breast Cancer.", "doi": "10.1007/s12012-023-09806-5", "pmid": "37684436", "authors": ["Daiqin Xiong", "Jianhua Yang", "Dongfeng Li", "Jie Wang"], "journal": "Cardiovascular toxicology", "year": 2023, "abstract": "Based on a few studies, heart failure patients with breast cancer were assessed to find potential biomarkers for doxorubicin-induced cardiotoxicity. However, key immune-related transcriptional markers linked to doxorubicin-induced cardiotoxicity in breast cancer patients have not been thoroughly investigated. We used GSE40447, GSE76314, and TCGA BRCA cohorts to perform this study. Then, we performed various bioinformatics approaches to identify the key immune-related transcriptional markers and their association with doxorubicin-induced cardiotoxicity in patients with breast cancer. We found 255 upregulated genes and 286 downregulated genes in patients with doxorubicin-induced heart failure in breast cancer. We discovered that in patients with breast cancer comorbidity doxorubicin-induced cardiotoxicity, the 58 immunological genes are elevated (such as CPA3, VSIG4, GATA2, RFX2, IL3RA, and LRP1), and the 60 genes are significantly suppressed (such as MS4A1, FCRL1, CD200, FCRLA, FCRL2, and CD79A). Furthermore, we revealed that the immune-related differentially expressed genes (DEGs) are substantially associated with the enrichment of KEGG pathways, including B-cell receptor signaling pathway, primary immunodeficiency, chemokine signaling pathway, hematopoietic cell lineage, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, MAPK signaling pathway, focal adhesion, dilated cardiomyopathy, cell adhesion molecule, etc. Moreover, we discovered that the doxorubicin-induced immune-related genes are crucially involved in the protein-protein interaction and gene clusters. The immune-related genes, including IFIT5, XCL1, SPIB, BTLA, MS4A1, CD19, TCL1A, CD83, CD200, FCRLA, CD79A, BIRC3, and IGF2R are significantly associated with a poor survival prognosis of breast cancer patients and showed diagnostic efficacy in patients with breast cancer and heart failure. Molecular docking revealed that the survival-associated genes interact with the doxorubicin with appreciable binding affinity. Finally, we validated the expression level of immune-related genes in breast cancer patients-derived cardiomyocytes with doxorubicin-induced cardiotoxicity and found that the level of RAD9A, HSPA1B, GATA2, IGF2R, CD200, ERCC8, and BCL11A genes are consistently dysregulated. Our findings offered a basis for understanding the mechanism and pathogenesis of the cardiotoxicity caused by doxorubicin in breast cancer patients and predicted the interaction of immune-related potential biomarkers with doxorubicin.", "claims": [{"id": "claim-method", "statement": "We used the R package limma to analyze differential expression in gene expression datasets [26].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37684436", "locator": "sections[4] \"Exploration of Doxorubicin-Induced Differentially Expressed Genes in Patients with Heart Failure and Breast Cancer\" paragraph 2", "quote": "We used the R package limma to analyze differential expression in gene expression datasets [26]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We used GSE40447, GSE76314, and TCGA BRCA cohorts for this study. We downloaded the GSE40447 and GSE76314 from the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). TCGA BRCA cohort was used from the GEPIA webserver.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37684436", "locator": "sections[27] \"notes\" paragraph 1", "quote": "We used GSE40447, GSE76314, and TCGA BRCA cohorts for this study. We downloaded the GSE40447 and GSE76314 from the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). TCGA BRCA cohort was used from the GEPIA webserver."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The immune-related genes, including IFIT5, XCL1, SPIB, BTLA, MS4A1, CD19, TCL1A, CD83, CD200, FCRLA, CD79A, BIRC3, and IGF2R are significantly associated with a poor survival prognosis of breast cancer patients and showed diagnostic efficacy in patients with breast cancer and heart failure.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37684436", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The immune-related genes, including IFIT5, XCL1, SPIB, BTLA, MS4A1, CD19, TCL1A, CD83, CD200, FCRLA, CD79A, BIRC3, and IGF2R are significantly associated with a poor survival prognosis of breast cancer patients and showed diagnostic efficacy in patients with breast cancer and heart failure."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The immune-related genes, including IFIT5, XCL1, SPIB, BTLA, MS4A1, CD19, TCL1A, CD83, CD200, FCRLA, CD79A, BIRC3, and IGF2R are significantly associated with a poor survival prognosis of breast cancer patients and showed diagnostic efficacy in patients with breast cancer and heart failure.", "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:37684436"], "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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