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通过加权基因共表达网络分析鉴定脓毒症诱导的心肌病潜在关键基因和浸润免疫细胞

Identification of Crucial Genes and Infiltrating Immune Cells Underlying Sepsis-Induced Cardiomyopathy via Weighted Gene Co-Expression Network Analysis.

作者信息

Li Juexing, Zhou Lei, Li Zhenhua, Yang Shangneng, Tang Liangyue, Gong Hui

机构信息

Department of Cardiology, Jinshan Hospital of Fudan University, Shanghai, China.

Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Front Genet. 2021 Dec 24;12:812509. doi: 10.3389/fgene.2021.812509. eCollection 2021.

Abstract

Sepsis-induced cardiomyopathy (SIC), with a possibly reversible cardiac dysfunction, is a potential complication of septic shock. Despite quite a few mechanisms including the inflammatory mediator, exosomes, and mitochondrial dysfunction, having been confirmed in the existing research studies we still find it obscure about the overall situation of gene co-expression that how they can affect the pathological process of SIC. Thus, we intended to find out the crucial hub genes, biological signaling pathways, and infiltration of immunocytes underlying SIC. It was weighted gene co-expression network analysis that worked as our major method on the ground of the gene expression profiles: hearts of those who died from sepsis were compared to hearts donated by non-failing humans which could not be transplanted for technical reasons (GSE79962). The top 25 percent of variant genes were abstracted to identify 10 co-expression modules. In these modules, brown and green modules showed the strongest negative and positive correlation with SIC, which were primarily enriched in the bioenergy metabolism, immunoreaction, and cell death. Next, nine genes (, , , , , , , , and ) including two downregulated and seven upregulated genes which were chosen as hub genes that meant the expressive level of which was higher than the counterparts in control groups. Then, the gene set enrichment analysis (GSEA) demonstrated a close relationship of hub genes to the cardiac metabolism and the necroptosis and apoptosis of cells in SIC. Concerning immune cells infiltration, a higher level of neutrophils and B cells native and a lower level of mast cells resting and plasma cells had been observed in patients with SIC. In general, nine candidate biomarkers were authenticated as a reliable signature for deeper exploration of basic and clinical research studies on SIC.

摘要

脓毒症诱导的心肌病(SIC)是脓毒性休克的一种潜在并发症,其心脏功能障碍可能是可逆的。尽管现有研究已证实包括炎症介质、外泌体和线粒体功能障碍在内的多种机制,但我们仍不清楚它们如何通过基因共表达影响SIC的病理过程。因此,我们旨在找出SIC潜在的关键枢纽基因、生物信号通路以及免疫细胞浸润情况。基于基因表达谱,加权基因共表达网络分析是我们的主要方法:将死于脓毒症患者的心脏与因技术原因无法移植的非衰竭人类捐献心脏(GSE79962)进行比较。提取变异基因排名前25%的基因以识别10个共表达模块。在这些模块中,棕色和绿色模块与SIC呈现出最强的负相关和正相关,主要富集在生物能量代谢、免疫反应和细胞死亡方面。接下来,九个基因(……此处原文九个基因未列出具体名称……)包括两个下调基因和七个上调基因被选为枢纽基因,意味着它们的表达水平高于对照组。然后,基因集富集分析(GSEA)表明枢纽基因与SIC中的心脏代谢以及细胞坏死性凋亡密切相关。关于免疫细胞浸润,在SIC患者中观察到较高水平的天然中性粒细胞和B细胞,以及较低水平的静息肥大细胞和浆细胞。总体而言,九个候选生物标志物被确认为一个可靠的特征,可用于对SIC进行更深入的基础和临床研究探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f96f/8740124/b94b6fa2114a/fgene-12-812509-g001.jpg

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