Bioinformatics and Immune Infiltration Analyses Reveal the Key Pathway and Immune Cells in the Pathogenesis of Hypertrophic Cardiomyopathy.
Bioinformatics and Immune Infiltration Analyses Reveal the Key Pathway and Immune Cells in the Pathogenesis of Hypertrophic Cardiomyopathy.
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DOI：
10.3389/fcvm.2021.696321
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发表时间：
2021
影响因子：
3.6
通讯作者：
Cheng X
中科院分区：
文献类型：
--
作者：
Zhang XZ;Zhang S;Tang TT;Cheng X
目的：本研究旨在通过生物信息学方法分析肥厚型心肌病（HCM）发病的关键通路和免疫细胞，探讨免疫浸润在HCM发病机制中的意义。研究方法：从GEO数据库获得来自人HCM和健康对照心脏组织的两个公共数据集（GSE 36961和GSE 141910）的表达谱。经数据预处理后，平行筛选HCM和健康对照心肌组织的差异表达基因（DEG）。使用大卫和GSEA应用程序进行基因本体、途径功能富集和基因集富集分析。HCM和对照心脏组织中免疫和基质细胞的组成模式基于使用xCell的合并数据进行估计。蛋白质相互作用（PPI）网络和模块分析的STRING和Cytoscape应用程序构建。基于性别的表达差异分析也进行了探讨HCM的性别差异。GSE 130036和临床样本用于验证分析。结果：共鉴定出310个DEG。DEGs表达上调主要集中在生物学过程中的“粘附”和“凋亡过程”。至于下调的DEG，“炎症反应”、“先天免疫反应”、“吞噬体”和“JAK-STAT信号通路”高度富集。免疫浸润分析显示，HCM组巨噬细胞、单核细胞、DC、Th 1、Treg和浆细胞评分显著降低，而CD 8 + T细胞、嗜碱性粒细胞、成纤维细胞和血小板显著富集。模块分析显示，STAT 3作为HCM的枢纽基因，与LYVE 1 + CD 163+巨噬细胞一起可能在HCM的发病机制中发挥关键作用，而在所选数据集的HCM样本中没有明显的性别差异。对GSE 130036和临床样本进行的验证分析显示LYVE 1和CD 163之间存在强正相关性（斯皮尔曼相关性= 0.7646）和良好的共定位关系，表明LYVE 1 + CD 163+巨噬细胞在维持心脏组织稳态中的潜在功能。结论：STAT 3相关通路和CD 163 + LYVE 1+巨噬细胞被确定为HCM的潜在关键通路和免疫细胞，并可能作为进一步深入研究的有趣靶点。
Objective: This study was designed to identify the key pathway and immune cells for hypertrophic cardiomyopathy (HCM) via bioinformatics analyses of public datasets and evaluate the significance of immune infiltration in the pathogenesis of HCM. Methods: Expressional profiling from two public datasets (GSE36961 and GSE141910) of human HCM and healthy control cardiac tissues was obtained from the GEO database. After data preprocessing, differentially expressed genes (DEGs) were then screened between HCM and healthy control cardiac tissues in parallel. Gene Ontology, pathway functional enrichment, and gene set enrichment analysis were performed using DAVID and GSEA application. The compositional patterns of immune and stromal cells in HCM and control cardiac tissues were estimated based on the merged data using xCell. Protein–protein interaction (PPI) network and module analyses were constructed by STRING and Cytoscape applications. Gender-based expressional differences analyses were also conducted to explore gender differences in HCM. GSE130036 and clinical samples were used for verification analyses. Results: A total of 310 DEGs were identified. Upregulated DEGs were mainly enriched in “adhesion” and “apoptotic process” in the biological process. As for the downregulated DEGs, “inflammatory response,” “innate immune response,” “phagosome,” and “JAK-STAT signaling pathway” were highly enriched. Immune infiltration analyses suggested that the scores of macrophages, monocytes, DC, Th1, Treg, and plasma cells in the HCM group were significantly decreased, while CD8+ T cells, basophils, fibroblasts, and platelets were significantly enriched. Module analyses revealed that STAT3, as the hub genes in HCM together with LYVE1+CD163+ macrophages, may play a key role in the pathogenesis of HCM while there were no obvious gender differences in the HCM samples from selected datasets. Verification analyses performed on GSE130036 and clinical samples showed a strong positive correlation (Spearman correlation = 0.7646) and a good co-localization relationship between LYVE1 and CD163, suggesting the potential function of LYVE1+CD163+ macrophages in maintaining the homeostasis of cardiac tissue. Conclusion: STAT3-related pathway and CD163+LYVE1+ macrophages were identified as the potential key pathway and immune cells in HCM and may serve as interesting targets for further in-depth research.