Department of Critical Care Medicine, Hubei Province Hospital of Traditional Chinese Medicine, 856 Luoyu Street, Wuhan, 430061, Hubei, People's Republic of China.
Hubei Province Academy of Traditional Chinese Medicine, 856 Luoyu Street, Wuhan, 430061, Hubei, People's Republic of China.
Sci Rep. 2023 Apr 17;13(1):6221. doi: 10.1038/s41598-023-33602-4.
Septic cardiomyopathy is a serious complication of sepsis. The mechanism of disease pathogenesis, which is caused by infection, is well researched. Despite ongoing efforts, there are no viable biological markers in the peripheral blood for early detection and diagnosis of septic cardiomyopathy. We aimed to uncover potential biomarkers of septic cardiomyopathy by comparing the covaried genes and pathways in the blood and myocardium of sepsis patients. Gene expression profiling of GSE79962, GSE65682, GSE54514, and GSE134364 was retrieved from the GEO database. Student's t-test was used for differential expression analysis. K-means clustering analysis was applied for subgroup identification. Least absolute shrinkage and selection operator (LASSO) and logistic regression were utilized for screening characteristic genes and model construction. Receiver operating characteristic (ROC) curves were generated for estimating the diagnostic efficacy. For ceRNA information prediction, miWalk and lncBase were applied. Cytoscape was used for ceRNA network construction. Inflammation-associated genes were upregulated, while genes related to mitochondria and aerobic metabolism were downregulated in both blood and the myocardium. Three groups with a significantly different mortality were identified by these covaried genes, using clustering analysis. Five characteristic genes-BCL2A1, CD44, ADGRG1, TGIF1, and ING3-were identified, which enabled the prediction of mortality of sepsis. The pathophysiological changes in the myocardium of patients with sepsis were also reflected in peripheral blood to some extent. The co-occurring pathological processes can affect the prognosis of sepsis. Thus, the genes we identified have the potential to become biomarkers for septic cardiomyopathy.
脓毒症性心肌病是脓毒症的严重并发症。由感染引起的疾病发病机制的机制已经得到了很好的研究。尽管在不断努力,但在外周血中仍没有用于早期检测和诊断脓毒性心肌病的可行的生物学标志物。我们旨在通过比较脓毒症患者血液和心肌中的变异基因和途径来发现脓毒性心肌病的潜在生物标志物。从 GEO 数据库中检索 GSE79962、GSE65682、GSE54514 和 GSE134364 的基因表达谱。使用学生 t 检验进行差异表达分析。应用 K-means 聚类分析进行亚组鉴定。最小绝对收缩和选择算子(LASSO)和逻辑回归用于筛选特征基因和模型构建。生成接收者操作特征(ROC)曲线以估计诊断效果。用于 ceRNA 信息预测,应用 miWalk 和 lncBase。使用 Cytoscape 构建 ceRNA 网络。炎症相关基因在血液和心肌中均上调,而与线粒体和有氧代谢相关的基因下调。通过聚类分析,这些变异基因可将死亡率明显不同的三组区分开来。确定了五个特征基因-BCL2A1、CD44、ADGRG1、TGIF1 和 ING3-,它们能够预测脓毒症的死亡率。脓毒症患者心肌的病理生理变化在一定程度上也反映在外周血中。同时发生的病理过程会影响脓毒症的预后。因此,我们鉴定的基因有可能成为脓毒性心肌病的生物标志物。