Xiong Ting, Xiao Botao, Wu Yueheng, Liu Yunfeng, Li Quhuan
School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, China.
Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, South China University of Technology, Guangzhou, China.
Front Cardiovasc Med. 2022 Apr 26;9:724262. doi: 10.3389/fcvm.2022.724262. eCollection 2022.
Coronary artery disease (CAD) is considered one of the leading causes of death worldwide. Although dysregulation of long non-coding RNAs (lncRNAs) has been reported to be associated with the initiation and progression of CAD, the knowledge regarding their specific functions as well their physiological/pathological significance in CAD is very limited. In this study, we aimed to systematically analyze immune-related lncRNAs in CAD and explore the relationship between key immune-related lncRNAs and the immune cell infiltration process. Based on differential expression analysis of mRNAs and lncRNAs, an immune-related lncRNA-mRNA weighted gene co-expression network containing 377 lncRNAs and 119 mRNAs was constructed. LINC01480 and AL359237.1 were identified as the hub immune-related lncRNAs in CAD using the random forest-recursive feature elimination and least absolute shrinkage and selection operator logistic regression. Furthermore, 93 CAD samples were divided into two subgroups according to the expression values of LINC01480 and AL359237.1 by consensus clustering analysis. By performing gene set enrichment analysis, we found that cluster 2 enriched more cardiovascular risk pathways than cluster 1. The immune cell infiltration analysis of ischemic cardiomyopathy (ICM; an advanced stage of CAD) samples revealed that the proportion of macrophage M2 was upregulated in the LINC01480 highly expressed samples, thus suggesting that LINC01480 plays a protective role in the progression of ICM. Based on the findings of this study, lncRNA LINC01480 may be used as a novel biomarker and therapeutic target for CAD.
冠状动脉疾病(CAD)被认为是全球主要的死亡原因之一。尽管已有报道称长链非编码RNA(lncRNA)的失调与CAD的发生和发展有关,但关于它们在CAD中的具体功能及其生理/病理意义的了解非常有限。在本研究中,我们旨在系统分析CAD中与免疫相关的lncRNA,并探讨关键免疫相关lncRNA与免疫细胞浸润过程之间的关系。基于mRNA和lncRNA的差异表达分析,构建了一个包含377个lncRNA和119个mRNA的免疫相关lncRNA-mRNA加权基因共表达网络。使用随机森林递归特征消除和最小绝对收缩与选择算子逻辑回归,将LINC01480和AL359237.1鉴定为CAD中关键的免疫相关lncRNA。此外,通过共识聚类分析,根据LINC01480和AL359237.1的表达值将93个CAD样本分为两个亚组。通过进行基因集富集分析,我们发现簇2比簇1富集了更多的心血管风险通路。对缺血性心肌病(ICM;CAD的晚期阶段)样本的免疫细胞浸润分析表明,在LINC01480高表达的样本中巨噬细胞M2的比例上调,这表明LINC01480在ICM的进展中起保护作用。基于本研究的结果,lncRNA LINC01480可能用作CAD的新型生物标志物和治疗靶点。