Table_4_Systematic analysis of myocardial immune progression in septic cardiomyopathy: Immune-related mechanisms in septic cardiomyopathy.xls

BackgroundThe immune infiltration and molecular mechanisms underlying septic cardiomyopathy (SC) have not been completely elucidated. This study aimed to identify key genes related to SC and elucidate the potential molecular mechanisms.
MethodsThe weighted correlation network analysis (WGCNA), linear models for microarray analysis (LIMMA), protein-protein interaction (PPI) network, CIBERSORT, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG), and gene set enrichment analysis (GSEA) were applied to assess the key pathway and hub genes involved in SC.
ResultsWe identified 10 hub genes, namely, LRG1, LCN2, PTX3, E LANE, TCN1, CLEC4D, FPR2, MCEMP1, CEACAM8, and CD177. Furthermore, we used GSEA for all genes and online tools to explore the function of the hub genes. Finally, we took the intersection between differential expression genes (DEGs) and hub genes to identify LCN2 and PTX3 as key genes. We found that immune-related pathways played vital roles in SC. LCN2 and PTX3 were key genes in SC progression, which mainly showed an anti-inflammatory effect. The significant immune cells in cardiomyocytes of SC were neutrophils and M2 macrophages.
ConclusionThese cells may have the potential to be prognostic and therapeutic targets in the clinical management of SC. Excessive anti-inflammatory function and neutrophil infiltration are probably the primary causes of SC.

背景：脓毒症心肌病（septic cardiomyopathy, SC）的免疫浸润现象与潜在分子机制尚未完全阐明。本研究旨在筛选与SC相关的关键基因，并阐明其潜在分子调控机制。
方法：本研究采用加权基因共表达网络分析（weighted correlation network analysis, WGCNA）、线性模型微阵列分析（linear models for microarray analysis, LIMMA）、蛋白质相互作用（protein-protein interaction, PPI）网络、CIBERSORT算法、京都基因与基因组百科全书通路（Kyoto Encyclopedia of Genes and Genomes pathway, KEGG）富集分析以及基因集富集分析（gene set enrichment analysis, GSEA），对SC相关的关键通路及核心基因进行鉴定与评估。
结果：本研究共筛选得到10个核心基因，分别为LRG1、LCN2、PTX3、ELANE、TCN1、CLEC4D、FPR2、MCEMP1、CEACAM8及CD177。随后，我们通过全基因GSEA分析及在线生物信息学工具对核心基因的功能进行了探究。最终，将差异表达基因（differential expression genes, DEGs）与核心基因取交集，最终确定LCN2与PTX3为SC关键基因。研究发现，免疫相关通路在SC发病进程中发挥至关重要的作用；LCN2及PTX3作为SC进展中的关键基因，主要表现出抗炎效应。SC患者心肌细胞中显著异常的免疫细胞为中性粒细胞与M2巨噬细胞。
结论：上述免疫细胞或可作为SC临床诊疗中的预后标志物与治疗靶点。过度抗炎功能与中性粒细胞浸润可能是SC发生的主要诱因。