Xu Xiang, Zou Renchao, Liu Xiaoyong, Liu Jia, Su Qianqian
Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China.
Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China.
Open Med (Wars). 2022 Apr 22;17(1):781-800. doi: 10.1515/med-2022-0476. eCollection 2022.
Epithelial-mesenchymal transition (EMT) is critical in the development of coronary artery disease (CAD). However, landscapes of EMT-related genes have not been fully established in CAD. We identified the differentially expressed mRNAs and lncRNAs (DElncRNAs) from the Gene Expression Omnibus database. Pearson's correlation analysis, the least absolute shrinkage and selection operator regression, and support vector machine reverse feature elimination algorithms were used to screen EMT-related lncRNAs. The cis-trans regulatory networks were constructed based on EMT-related lncRNAs. Quantitative real-time polymerase chain reaction was performed to validate the expression of EMT-related genes in a cohort of six patients with CAD and six healthy controls. We further estimated the infiltration of the immune cells in CAD patients with five algorithms, and the correlation between EMT-related genes and infiltrating immune cells was analyzed. We identified eight EMT-related lncRNAs in CAD. The area under curve value was greater than 0.95. The immune analysis revealed significant CD8 T cells, monocytes, and NK cells in CAD and found that EMT-related lncRNAs were correlated with these immune cell subsets. Moreover, SNAI2, an EMT-TF gene, was found in the trans-regulatory network of EMT-related lncRNAs. Further, we found SNAI2 as a biomarker for the diagnosis of CAD but it also had a close correlation with immune cell subsets in CAD. Eight EMT-related lncRNAs and SNAI2 have important significance in the diagnosis of CAD patients.
上皮-间质转化（EMT）在冠状动脉疾病（CAD）的发展中至关重要。然而，CAD中EMT相关基因的情况尚未完全明确。我们从基因表达综合数据库中鉴定出差异表达的mRNA和lncRNA（DElncRNAs）。使用Pearson相关分析、最小绝对收缩和选择算子回归以及支持向量机反向特征消除算法筛选EMT相关lncRNAs。基于EMT相关lncRNAs构建顺式-反式调控网络。进行定量实时聚合酶链反应以验证6例CAD患者和6例健康对照队列中EMT相关基因的表达。我们进一步用五种算法估计CAD患者中免疫细胞的浸润情况，并分析EMT相关基因与浸润免疫细胞之间的相关性。我们在CAD中鉴定出8个EMT相关lncRNAs。曲线下面积值大于0.95。免疫分析显示CAD中有显著的CD8 T细胞、单核细胞和NK细胞，并发现EMT相关lncRNAs与这些免疫细胞亚群相关。此外，在EMT相关lncRNAs的反式调控网络中发现了EMT-TF基因SNAI2。进一步地，我们发现SNAI2可作为CAD诊断的生物标志物，而且它与CAD中的免疫细胞亚群也密切相关。8个EMT相关lncRNAs和SNAI2在CAD患者的诊断中具有重要意义。
