据少数研究显示，对乳腺癌患者进行评估以寻找多柔比星诱导心脏毒性的潜在生物标志物。然而，与乳腺癌患者多柔比星诱导心脏毒性相关的关键免疫相关转录标记尚未得到深入研究。我们使用了GSE40447、GSE76314和TCGA BRCA队列来进行本研究。然后，我们采用多种生物信息学方法来确定关键的免疫相关转录标记及其与乳腺癌患者多柔比星诱导心脏毒性的关联。我们发现乳腺癌患者多柔比星诱导心力衰竭时有255个上调基因和286个下调基因。我们发现，在合并乳腺癌和多柔比星诱导心脏毒性的患者中，有58个免疫相关基因升高（如CPA3、VSIG4、GATA2、RFX2、IL3RA和LRP1），有60个基因显著抑制（如MS4A1、FCRL1、CD200、FCRLA、FCRL2和CD79A）。此外，我们还发现，这些免疫相关差异表达基因（DEGs）与KEGG通路的富集显著相关，包括B细胞受体信号通路、原发性免疫缺陷、趋化因子信号通路、造血细胞系分化、细胞因子-细胞因子受体相互作用、Toll样受体信号通路、MAPK信号通路、黏附斑、扩张型心肌病、细胞黏附分子等。此外，我们还发现多柔比星诱导的免疫相关基因在蛋白质相互作用和基因簇中起到了重要作用。这些与生存相关的免疫相关基因，如IFIT5、XCL1、SPIB、BTLA、MS4A1、CD19、TCL1A、CD83、CD200、FCRLA、CD79A、BIRC3和IGF2R，与乳腺癌患者的生存预后显著相关，并在乳腺癌和心衰患者中显示了诊断效能。分子对接揭示了这些与生存相关基因与多柔比星之间可观的结合亲和力。最后，我们验证了乳腺癌患者派生心肌细胞中免疫相关基因的表达水平，并发现RAD9A、HSPA1B、GATA2、IGF2R、CD200、ERCC8和BCL11A基因的表达一致受到调节。我们的研究结果为理解乳腺癌患者多柔比星引起的心脏毒性的机制和发病机理提供了基础，并预测了与多柔比星的免疫相关潜在生物标志物的相互作用。© 2023. 作者们。

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.© 2023. The Author(s).