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

• DOI: 10.1007/s12012-023-09806-5
• Publication Date: 2023-09-08T17:01:52Z
• Authors: Daiqin Xiong; Jianhua Yang; Dongfeng Li; Jie Wang
• Keywords: Cardiotoxicity; BTLA

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 cardiotoxicity in have not been thoroughly investigated. We used GSE40447, GSE76314, and TCGA BRCA cohorts perform this study. Then, we performed various bioinformatics approaches identify the their association cancer. found 255 upregulated genes 286 downregulated discovered that comorbidity cardiotoxicity, 58 immunological are elevated (such as CPA3, VSIG4, GATA2, RFX2, IL3RA, LRP1), 60 significantly suppressed MS4A1, FCRL1, CD200, FCRLA, FCRL2, CD79A). Furthermore, revealed differentially expressed (DEGs) substantially associated enrichment of KEGG pathways, including B-cell receptor signaling pathway, primary immunodeficiency, chemokine hematopoietic cell lineage, cytokine-cytokine interaction, Toll-like MAPK focal adhesion, dilated cardiomyopathy, adhesion molecule, etc. Moreover, crucially involved protein-protein interaction gene clusters. The genes, IFIT5, XCL1, SPIB, BTLA, CD19, TCL1A, CD83, CD79A, BIRC3, IGF2R poor survival prognosis showed diagnostic efficacy failure. Molecular docking survival-associated interact doxorubicin appreciable binding affinity. Finally, validated expression level patients-derived cardiomyocytes RAD9A, HSPA1B, IGF2R, ERCC8, BCL11A consistently dysregulated. Our findings offered basis understanding mechanism pathogenesis caused by predicted doxorubicin.