Wang Haiming, Shao Junjie, Lu Xuechun, Jiang Min, Li Xin, Liu Zifan, Zhao Yunzhang, Zhou Jingjing, Lin Lejian, Wang Lin, Xu Qiang, Chen Yundai, Zhang Ran
Department of Cardiovascular Medicine, Chinese PLA General Hospital and Chinese People's Liberation Army (PLA) Medical School, Beijing, China.
Department of Hematology, The Second Medical Center of Chinese PLA General Hospital and Chinese People's Liberation Army (PLA) Medical School, Beijing, China.
Front Cardiovasc Med. 2022 Aug 26;9:893502. doi: 10.3389/fcvm.2022.893502. eCollection 2022.
Coronary heart disease (CHD) is the most common progressive disease that is difficult to diagnose and predict in the young asymptomatic period. Our study explored a mechanistic understanding of the genetic effects of premature CHD (PCHD) and provided potential biomarkers and treatment targets for further research through high throughput sequencing and integrated bioinformatics analysis.
High throughput sequencing was performed among recruited patients with PCHD and young healthy individuals, and CHD-related microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using R software. Enrichment analysis and CIBERSORT were performed to explore the enriched pathways of DEGs and the characteristics of infiltrating immune cells. Hub genes identified by protein-protein interaction (PPI) networks were used to construct the competitive endogenous RNA (ceRNA) networks. Potential drugs were predicted by using the Drug Gene Interaction Database (DGIdb).
A total of 35 DEGs were identified from the sequencing dataset and GEO database by the Venn Diagram. Enrichment analysis indicated that DEGs are mostly enriched in excessive immune activation pathways and signal transduction. CIBERSORT exhibited that resting memory CD4 T cells and neutrophils were more abundant, and M2 macrophages, CD8 T cells, and naïve CD4 T cells were relatively scarce in patients with PCHD. After the identification of 10 hub gens, three ceRNA networks of , and were constructed by data retrieval and validation. In addition, might interact most with multiple chemical compounds mainly consisting of anti-inflammatory drugs.
The immune dysfunction mainly contributes to the pathogenesis of PCHD, and three ceRNA networks of , and may be potential candidate biomarkers for early diagnosis and treatment targets of PCHD.
冠心病（CHD）是最常见的进展性疾病，在年轻无症状期难以诊断和预测。我们的研究通过高通量测序和综合生物信息学分析，探索了早发性冠心病（PCHD）遗传效应的机制理解，并为进一步研究提供了潜在的生物标志物和治疗靶点。
对招募的PCHD患者和年轻健康个体进行高通量测序，并从基因表达综合数据库（GEO）中获取与CHD相关的微阵列数据集。使用R软件鉴定差异表达基因（DEG）。进行富集分析和CIBERSORT分析，以探索DEG的富集途径和浸润免疫细胞的特征。通过蛋白质-蛋白质相互作用（PPI）网络鉴定的枢纽基因用于构建竞争性内源性RNA（ceRNA）网络。使用药物基因相互作用数据库（DGIdb）预测潜在药物。
通过维恩图从测序数据集和GEO数据库中总共鉴定出35个DEG。富集分析表明，DEG大多富集于过度免疫激活途径和信号转导。CIBERSORT分析显示，PCHD患者中静息记忆CD4 T细胞和中性粒细胞较多，而M2巨噬细胞、CD8 T细胞和幼稚CD4 T细胞相对较少。在鉴定出10个枢纽基因后，通过数据检索和验证构建了三个ceRNA网络，分别为 、 和 。此外， 可能与主要由抗炎药物组成的多种化合物相互作用最多。
免疫功能障碍主要促成PCHD的发病机制， 、 和 这三个ceRNA网络可能是PCHD早期诊断的潜在候选生物标志物和治疗靶点。
