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缺血性心肌病与扩张型心肌病之间T细胞相关血清标志物的差异。

Differences in T cell-associated serum markers between ischemic cardiomyopathy and dilated cardiomyopathy.

作者信息

Huang Yuli, Xuan Lin, Xu Qiong, Wang Jun, Liu Jie

机构信息

Department of Cardiovascular Medicine, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.

Department of Internal Medicine, Suixi County Hospital of Traditional Chinese Medicine, Huaibei, China.

出版信息

J Thorac Dis. 2024 Jul 30;16(7):4655-4665. doi: 10.21037/jtd-24-901. Epub 2024 Jul 26.

Abstract

BACKGROUND

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) have similar clinical manifestations but differ in pathogenesis. We aimed to identify T cell-associated serum markers that can be used to distinguish between ICM and DCM.

METHODS

We identified differentially expressed genes (DEGs) with transcriptome sequencing data in GSE116250, and then conducted enrichment analysis of DEGs in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein-protein interaction (PPI) networks were used to analyze the relationship between T cells-related genes and identify hub genes. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect T cell-associated proteins in serum, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of these serum markers.

RESULTS

Using the limma package and Venn plots, we found that the non-failing donors (NFD) and DCM groups shared many of the same DEGs and DEGs-enriched functions compared to the ICM group, which were involved in T cell activation and differentiation, among other functions. Subsequently, the immune cell score showed no difference between NFD and DCM, but they were significantly different from ICM patients in CD8 T cells CD4 T cells memory resting and activated, T cells follicular helper, and M1 macrophage. After analyzing T cell-associated DEGs, it was found that 4 DEGs encoding secreted proteins were highly expressed in the ICM group compared with the NFD and DCM groups, namely chemokine (C-C motif) ligand 21 (), interleukin () lymphocyte-activation gene 3 (), and vascular cell adhesion molecule-1 (). Importantly, the serum levels of , , , and in ICM patients were all significantly higher than those in DCM patients. The ROC curves showed that the area under the curve (AUC) values of serum , , , and were 0.775, 0.868, 0.934, and 0.903, respectively.

CONCLUSIONS

We have identified four T cell-associated serum markers, , , , and , as potential diagnostic serum markers that differentiate ICM from DCM.

摘要

背景

缺血性心肌病(ICM)和扩张型心肌病(DCM)临床表现相似,但发病机制不同。我们旨在鉴定可用于区分ICM和DCM的T细胞相关血清标志物。

方法

我们利用GSE116250中的转录组测序数据鉴定差异表达基因(DEG),然后在基因本体论(GO)和京都基因与基因组百科全书(KEGG)数据库中对DEG进行富集分析。利用蛋白质-蛋白质相互作用(PPI)网络分析T细胞相关基因之间的关系并鉴定枢纽基因。使用酶联免疫吸附测定(ELISA)试剂盒检测血清中T细胞相关蛋白,并使用受试者工作特征(ROC)曲线评估这些血清标志物的诊断效能。

结果

使用limma软件包和维恩图,我们发现与ICM组相比,非衰竭供体(NFD)组和DCM组共享许多相同的DEG和DEG富集功能,这些功能涉及T细胞活化和分化等。随后,免疫细胞评分显示NFD和DCM之间无差异,但在CD8 T细胞、CD4 T细胞、静息和活化记忆T细胞、滤泡辅助性T细胞和M1巨噬细胞方面,它们与ICM患者有显著差异。在分析T细胞相关DEG后,发现与NFD组和DCM组相比,4个编码分泌蛋白的DEG在ICM组中高表达,即趋化因子(C-C基序)配体21()、白细胞介素()、淋巴细胞激活基因3()和血管细胞黏附分子1()。重要的是,ICM患者血清中、、和的水平均显著高于DCM患者。ROC曲线显示,血清、、和的曲线下面积(AUC)值分别为0.775、0.868、0.934和0.903。

结论

我们已鉴定出4种T细胞相关血清标志物、、和,作为区分ICM与DCM的潜在诊断血清标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1190/11320225/d6441cdc7791/jtd-16-07-4655-f1.jpg

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