The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, 570100, People's Republic of China.
The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, 550001, People's Republic of China.
Sci Rep. 2023 Jul 13;13(1):11358. doi: 10.1038/s41598-023-32992-9.
Sepsis is the uncontrolled reaction of the body to infection-induced inflammation, which results in life-threatening multiple-organ dysfunction (MODS). Although the research on sepsis has advanced significantly in recent years, its pathophysiology remains entirely unknown. Ferroptosis is a new-fashioned type of programmed cell death that may have an impact on sepsis development. However, the precise mechanism still needs to be explored. In this paper, Four pediatric sepsis datasets [training datasets (GSE26378 and GSE26440) and validation datasets (GSE11755 and GSE11281)] were chosen through the GEO (Gene Expression Omnibus) database, and 63 differentially expressions of ferroptosis-relation-genes (DE-FRGs) were eventually discovered using bioinformatics investigation. Functional annotation was performed using GO and KEGG pathway enrichment analysis. Then, four Core-FRGs (FTH1, GPX4, ACSL1, and ACSL6) were extracted after the construction of the protein-protein interaction (PPI) network and the research of the MCODE module. Consequently, Hub-FRG (GPX4) was found using the validation datasets, and correlation exploration of immunity populations (neutrophils, r = - 0.52; CD8 T-cells, r = 0.43) and immunity checkpoints (CD274, r = - 0.42) was implemented. The usefulness of GPX4 as a marker in sepsis was assessed in a mouse model of sepsis. The findings demonstrate that GPX4 is a crucial biomarker and a new latent immunotherapy target for the prediction and therapy of pediatric sepsis.
脓毒症是机体对感染引起的炎症反应失控，导致危及生命的多器官功能障碍（MODS）。尽管近年来对脓毒症的研究有了显著进展，但它的病理生理学仍然完全未知。铁死亡是一种新型的程序性细胞死亡，可能对脓毒症的发展有影响。然而，确切的机制仍需要探索。在本文中，通过 GEO（基因表达综合数据库）数据库选择了四个儿科脓毒症数据集[训练数据集（GSE26378 和 GSE26440）和验证数据集（GSE11755 和 GSE11281）]，并使用生物信息学研究最终发现了 63 个铁死亡相关基因（DE-FRGs）的差异表达。使用 GO 和 KEGG 通路富集分析进行功能注释。然后，在构建蛋白质-蛋白质相互作用（PPI）网络和研究 MCODE 模块后，提取了四个核心-FRGs（FTH1、GPX4、ACSL1 和 ACSL6）。随后，使用验证数据集找到了枢纽-FRG（GPX4），并对免疫群体（中性粒细胞，r=−0.52；CD8 T 细胞，r=0.43）和免疫检查点（CD274，r=−0.42）进行相关性探索。在脓毒症的小鼠模型中评估了 GPX4 作为标志物的有用性。研究结果表明，GPX4 是预测和治疗儿科脓毒症的一个关键生物标志物和一个新的潜在免疫治疗靶点。
