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Identification of the Key Genes of Immune Infiltration in Dilated Cardiomyopathy
International Heart Journal ( IF 1.5 ) Pub Date : 2023-11-30 , DOI: 10.1536/ihj.23-182
Bin Qi 1 , Hai-Yan Wang 1 , Xiao Ma 1 , Yu-Feng Chi 1 , Chun Gui 1
Affiliation  

Dilated cardiomyopathy (DCM) is a common cause of heart failure. In this study, we screened the immune infiltration-related genes associated with DCM to explore the potential molecular mechanisms and provide a basis for the early diagnosis and development of new immunotherapeutic targets. A dataset related to DCM was downloaded from the Gene Expression Omnibus (GEO) database. R software was applied to the genetic differential analysis of patients with DCM and healthy individuals, and the obtained differential expressed genes (DEGs) were screened for differentially expressed immune-related genes (DEIRGs) after comparison with the immune microsatellite database. Gene functional analysis established a protein interaction network (PPI). The immune infiltration in patients with DCM versus normal controls was assessed using the CIBERSORT algorithm, the hub genes were screened using the MOCDE app, and the hubs were validated in multiple datasets. A total of 246 DEGs were screened (adj. P < 0.05 and |logFC| > 0.3), and a total of 170 DEIRGs were compared. Gene Ontology analysis showed significant (adj. P < 0.05) Biological Process entries of 591, Cellular Component of 10, and Molecular Function of 39; Kyoto Encyclopedia of Genes and Genomes showed 20 significant entries, mainly focused on cytokines involved in immune-related response, etc. A protein interaction network comprising 28 hub DEGs was constructed in combination with the PPI network interactions. DEIRG was mainly distributed in the T-cell receptor pathway by immune infiltration detection analysis, and significant changes in central memory T-cells were found by analyzing T-cell-related subpathways, where INSR, HLA-B, IFITM1, and HBEGF were significantly differentially expressed. We selected 632 hospitalized patients for validation and found that INSR and HLA-B expression were associated with DCM development by Nomogram. The expression of HLA-B in peripheral blood T-cells was higher in DCM patients than in the normal group, as verified by qRT-PCR. However, the detailed mechanism needs to be further explored.



中文翻译:

扩张型心肌病免疫浸润关键基因的鉴定

扩张型心肌病(DCM)是心力衰竭的常见原因。在本研究中,我们筛选了与DCM相关的免疫浸润相关基因,探讨其潜在的分子机制,为早期诊断和开发新的免疫治疗靶点提供依据。从基因表达综合 (GEO) 数据库下载与 DCM 相关的数据集。应用R软件对DCM患者与健康个体进行遗传差异分析,将获得的差异表达基因(DEGs)与免疫微卫星数据库进行比对,筛选差异表达免疫相关基因(DEIRGs)。基因功能分析建立了蛋白质相互作用网络(PPI)。使用 CIBERSORT 算法评估 DCM 患者与正常对照的免疫浸润,使用 MOCDE 应用程序筛选中枢基因,并在多个数据集中验证中枢基因。总共筛选了 246 个 DEG(调整P < 0.05 和 |logFC| > 0.3),并比较了总共 170 个 DEIRG。基因本体分析显示显着的(调整P < 0.05)生物过程条目为 591 个,细胞成分为 10 个,分子功能为 39 个;京都基因与基因组百科全书显示了20个重要条目,主要集中在参与免疫相关反应的细胞因子等。结合PPI网络相互作用,构建了包含28个枢纽DEG的蛋白质相互作用网络。免疫浸润检测分析DEIRG主要分布在T细胞受体通路,通过分析T细胞相关亚通路发现中枢记忆T细胞发生显着变化,其中INSRHLA-BIFITM1HBEGF显着变化。差异表达。我们选取了 632 名住院患者进行验证,通过列线图发现INSRHLA-B表达与 DCM 发展相关。qRT-PCR证实,DCM患者外周血T细胞中HLA-B的表达高于正常组。但具体机制还需要进一步探讨。

更新日期:2023-12-02
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