Zhang Xu-Zhe, Zhang Si, Tang Ting-Ting, Cheng Xiang
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan, China.
Front Cardiovasc Med. 2021 Aug 23;8:696321. doi: 10.3389/fcvm.2021.696321. eCollection 2021.
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. 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. 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 LYVE1CD163 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 LYVE1CD163 macrophages in maintaining the homeostasis of cardiac tissue. STAT3-related pathway and CD163LYVE1 macrophages were identified as the potential key pathway and immune cells in HCM and may serve as interesting targets for further in-depth research.
本研究旨在通过对公共数据集的生物信息学分析，确定肥厚型心肌病（HCM）的关键通路和免疫细胞，并评估免疫浸润在HCM发病机制中的意义。从GEO数据库中获取了来自人类HCM和健康对照心脏组织的两个公共数据集（GSE36961和GSE141910）的表达谱。经过数据预处理后，并行筛选HCM和健康对照心脏组织之间的差异表达基因（DEG）。使用DAVID和GSEA应用程序进行基因本体论、通路功能富集和基因集富集分析。基于合并数据，使用xCell估计HCM和对照心脏组织中免疫细胞和基质细胞的组成模式。通过STRING和Cytoscape应用程序构建蛋白质-蛋白质相互作用（PPI）网络和模块分析。还进行了基于性别的表达差异分析，以探索HCM中的性别差异。使用GSE130036和临床样本进行验证分析。共鉴定出310个DEG。上调的DEG主要在生物学过程中的“黏附”和“凋亡过程”中富集。至于下调的DEG，“炎症反应”、“固有免疫反应”、“吞噬体”和“JAK-STAT信号通路”高度富集。免疫浸润分析表明，HCM组中巨噬细胞、单核细胞、树突状细胞、Th1、调节性T细胞和浆细胞的评分显著降低，而CD8 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，STAT3与LYVE1+CD163巨噬细胞一起作为HCM中的枢纽基因，可能在HCM的发病机制中起关键作用，而所选数据集中的HCM样本没有明显的性别差异。对GSE130036和临床样本进行的验证分析显示，LYVE1和CD163之间存在强正相关（Spearman相关性=0.7646）和良好的共定位关系，表明LYVE1+CD163巨噬细胞在维持心脏组织稳态中的潜在功能。STAT3相关通路和CD163+LYVE1巨噬细胞被确定为HCM中的潜在关键通路和免疫细胞，可能作为进一步深入研究的有趣靶点。
