T cell‒mediated rejection (TCMR) and antibody‐mediated rejection (ABMR) are severe post‐transplantation complications for heart transplantation (HTx), whose molecular and immunological pathogenesis remains unclear. In the present study, the mRNA microarray data set GSE124897 containing 645 stable, 52 TCMR and 144 ABMR endomyocardial biopsies was obtained to screen for differentially expressed genes (DEGs) between rejected and stable HTx samples and to investigate immune cell infiltration. Functional enrichment analyses indicated roles of the DEGs primarily in immune‐related mechanisms. Protein‐protein interaction networks were then constructed, and ICAM1, CD44, HLA‐A and HLA‐B were identified as hub genes using the maximal clique centrality method. Immune cell infiltration analysis revealed differences in adaptive and innate immune cell populations between TCMR, ABMR and stable HTx samples. Additionally, hub gene expression levels significantly correlated with the degree and composition of immune cell infiltration in HTx rejection samples. Furthermore, drug‐gene interactions were constructed, and 12 FDA‐approved drugs were predicted to target hub genes. Finally, an external GSE2596 data set was used to validate the expression of the hub genes, and ROC curves indicated all four hub genes had promising diagnostic value for HTx rejection. This study provides a comprehensive perspective of molecular and immunological regulatory mechanisms underlying HTx rejection.

中文翻译：

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心内膜心肌活检对心脏移植排斥反应中枢纽基因和免疫状态的研究

T细胞介导的排斥（TCMR）和抗体介导的排斥（ABMR）是心脏移植（HTx）的严重移植后并发症，其分子和免疫发病机制尚不清楚。在本研究中，获得了包含 645 个稳定、52 个 TCMR 和 144 个 ABMR 心内膜活检的 mRNA 微阵列数据集 GSE124897，以筛选被拒绝和稳定的 HTx 样本之间的差异表达基因 (DEG)，并研究免疫细胞浸润。功能富集分析表明 DEG 主要在免疫相关机制中的作用。然后构建蛋白质-蛋白质相互作用网络，ICAM1、CD44、HLA-A和HLA-B使用最大集团中心性方法将其鉴定为枢纽基因。免疫细胞浸润分析揭示了 TCMR、ABMR 和稳定 HTx 样本之间适应性和先天免疫细胞群的差异。此外，hub 基因表达水平与 HTx 排斥样品中免疫细胞浸润的程度和组成显着相关。此外，构建了药物-基因相互作用，并预测了 12 种 FDA 批准的药物靶向中枢基因。最后，使用外部 GSE2596 数据集验证 hub 基因的表达，ROC 曲线表明所有四个 hub 基因都具有良好的 HTx 排斥诊断价值。这项研究提供了 HTx 排斥背后的分子和免疫调节机制的综合视角。