School of Medicine, South China University of Technology, Guangzhou, China.
The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Biomed Res Int. 2021 Oct 15;2021:3440498. doi: 10.1155/2021/3440498. eCollection 2021.
Coronary heart disease (CHD) is the most prevalent disease with an unelucidated pathogenetic mechanism and is mediated by complex molecular interactions of exosomes. Here, we aimed to identify differentially expressed exosome genes for the disease development and prognosis of CHD.
Six CHD samples and 32 normal samples were downloaded from the exoRbase database to identify the candidate genes in the CHD. The differentially expressed genes (DEGs) were identified. And then, weighted gene correlation network analysis (WGCNA) was used to investigate the modules in coexpressed genes between CHD samples and normal samples. DEGs and the module of the WGCNA were intersected to obtain the most relevant exosome genes. After that, the function enrichment analyses and protein-protein interaction network (PPI) were performed for the particular module using STRING and Cytoscape software. Finally, the CIBERSORT algorithm was used to analyze the immune infiltration of exosome genes between CHD samples and normal samples.
We obtain a total of 715 overlapping exosome genes located at the intersection of the DEGs and key modules. The Gene Ontology enrichment of DEGs in the blue module included inflammatory response, neutrophil degranulation, and activation of CHD. In addition, protein-protein networks were constructed, and hub genes were identified, such as LYZ, CAMP, HP, ORM1, and LTF. The immune infiltration profiles varied significantly between normal controls and CHD. Finally, we found that mast cells activated and eosinophils had a positive correlation. B cell memory had a significant negative correlation with B cell naive. Besides, neutrophils and mast cells were significantly increased in CHD patients.
The underlying mechanism may be related to neutrophil degranulation and the immune response. The hub genes and the difference in immune infiltration identified in the present study may provide new insights into the diagnostic and provide candidate targets for CHD.
冠心病（CHD）是最常见的疾病，其发病机制尚未阐明，是由外泌体复杂的分子相互作用介导的。在这里，我们旨在确定差异表达的外泌体基因，用于 CHD 的疾病发展和预后。
从 exoRbase 数据库中下载了 6 个 CHD 样本和 32 个正常样本，以鉴定 CHD 中的候选基因。鉴定差异表达基因（DEGs）。然后，使用加权基因相关网络分析（WGCNA）研究 CHD 样本和正常样本之间共表达基因的模块。将 DEGs 和 WGCNA 的模块进行交集，获得最相关的外泌体基因。之后，使用 STRING 和 Cytoscape 软件对特定模块进行功能富集分析和蛋白质-蛋白质相互作用网络（PPI）分析。最后，使用 CIBERSORT 算法分析 CHD 样本和正常样本中外泌体基因的免疫浸润。
我们获得了总共 715 个重叠的外泌体基因，位于 DEGs 和关键模块的交集处。蓝色模块中 DEGs 的基因本体论富集包括炎症反应、中性粒细胞脱颗粒和 CHD 激活。此外，构建了蛋白质-蛋白质网络，并鉴定了关键基因，如 LYZ、CAMP、HP、ORM1 和 LTF。正常对照组和 CHD 之间的免疫浸润谱差异显著。最后，我们发现激活的肥大细胞和嗜酸性粒细胞呈正相关。B 细胞记忆与 B 细胞原始细胞呈显著负相关。此外，CHD 患者中性粒细胞和肥大细胞明显增加。
潜在机制可能与中性粒细胞脱颗粒和免疫反应有关。本研究中鉴定的关键基因和免疫浸润差异可能为 CHD 的诊断提供新的见解，并提供 CHD 的候选靶点。
