Li Jingru, Sun Guihu, Ma Haocheng, Wu Xinyu, Li Chaozhong, Ding Peng, Lu Si, Li Yanyan, Yang Ping, Li Chaguo, Yang Jun, Peng Yunzhu, Meng Zhaohui, Wang Luqiao
Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Emergency, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Front Cardiovasc Med. 2022 Sep 20;9:971543. doi: 10.3389/fcvm.2022.971543. eCollection 2022.
Septic cardiomyopathy (SCM) is a serious complication caused by sepsis that will further exacerbate the patient's prognosis. However, immune-related genes (IRGs) and their molecular mechanism during septic cardiomyopathy are largely unknown. Therefore, our study aims to explore the immune-related hub genes (IRHGs) and immune-related miRNA-mRNA pairs with potential biological regulation in SCM by means of bioinformatics analysis and experimental validation.
Firstly, screen differentially expressed mRNAs (DE-mRNAs) from the dataset GSE79962, and construct a PPI network of DE-mRNAs. Secondly, the hub genes of SCM were identified from the PPI network and the hub genes were overlapped with immune cell marker genes (ICMGs) to further obtain IRHGs in SCM. In addition, receiver operating characteristic (ROC) curve analysis was also performed in this process to determine the disease diagnostic capability of IRHGs. Finally, the crucial miRNA-IRHG regulatory network of IRHGs was predicted and constructed by bioinformatic methods. Real-time quantitative reverse transcription-PCR (qRT-PCR) and dataset GSE72380 were used to validate the expression of the key miRNA-IRHG axis.
The results of immune infiltration showed that neutrophils, Th17 cells, Tfh cells, and central memory cells in SCM had more infiltration than the control group; A total of 2 IRHGs were obtained by crossing the hub gene with the ICMGs, and the IRHGs were validated by dataset and qRT-PCR. Ultimately, we obtained the IRHG in SCM: THBS1. The ROC curve results of THBS1 showed that the area under the curve (AUC) was 0.909. Finally, the miR-222-3p/THBS1 axis regulatory network was constructed.
In summary, we propose that THBS1 may be a key IRHG, and can serve as a biomarker for the diagnosis of SCM; in addition, the immune-related regulatory network miR-222-3p/THBS1 may be involved in the regulation of the pathogenesis of SCM and may serve as a promising candidate for SCM therapy.
脓毒症性心肌病（SCM）是脓毒症引起的一种严重并发症，会进一步恶化患者的预后。然而，脓毒症性心肌病期间的免疫相关基因（IRG）及其分子机制在很大程度上尚不清楚。因此，我们的研究旨在通过生物信息学分析和实验验证，探索脓毒症性心肌病中具有潜在生物学调节作用的免疫相关枢纽基因（IRHG）和免疫相关miRNA-mRNA对。
首先，从数据集GSE79962中筛选差异表达的mRNA（DE-mRNA），并构建DE-mRNA的蛋白质-蛋白质相互作用（PPI）网络。其次，从PPI网络中鉴定出脓毒症性心肌病的枢纽基因，并将枢纽基因与免疫细胞标记基因（ICMG）进行重叠，以进一步获得脓毒症性心肌病中的免疫相关枢纽基因。此外，在此过程中还进行了受试者工作特征（ROC）曲线分析，以确定免疫相关枢纽基因的疾病诊断能力。最后，通过生物信息学方法预测并构建免疫相关枢纽基因的关键miRNA-IRHG调控网络。使用实时定量逆转录PCR（qRT-PCR）和数据集GSE72380验证关键miRNA-IRHG轴的表达。
免疫浸润结果显示，脓毒症性心肌病中的中性粒细胞、Th17细胞、滤泡辅助性T细胞和中央记忆细胞比对照组有更多的浸润；通过将枢纽基因与免疫细胞标记基因交叉共获得2个免疫相关枢纽基因，并通过数据集和qRT-PCR对免疫相关枢纽基因进行了验证。最终，我们获得了脓毒症性心肌病中的免疫相关枢纽基因：THBS1。THBS1的ROC曲线结果显示曲线下面积（AUC）为0.909。最后，构建了miR-222-3p/THBS1轴调控网络。
综上所述，我们提出THBS1可能是一个关键的免疫相关枢纽基因，可作为脓毒症性心肌病诊断的生物标志物；此外，免疫相关调控网络miR-222-3p/THBS1可能参与脓毒症性心肌病发病机制的调控，并可能成为脓毒症性心肌病治疗的有希望的候选靶点。
