PDF(Pubmed)
Abstract：
Ischemia-reperfusion injury (IRI) is inevitable in kidney transplantations and, as a complex pathophysiological process, it can be greatly impacted by ferroptosis and immune inflammation. Our study aimed to identify the biomarkers of renal IRI (RIRI) and elucidate their relationship with immune infiltration. In this study, the GSE148420 database was used as a training set to analyze differential genes and overlap them with ferroptosis-related genes to identify hub genes using a protein-protein interaction (PPI) network, the least absolute shrinkage and selection operator (LASSO), and random forest algorithm (RFA). We verified the hub gene and ferroptosis-related phenotypes in a verification set and animal experiments involving unilateral IRI with contralateral nephrectomy in rats. Gene set enrichment analysis (GSEA) of single genes was conducted according to the hub gene to predict related endogenous RNAs (ceRNAs) and drugs to establish a network. Finally, we used the Cibersort to analyze immunological infiltration and conducted Spearman\'s correlation analysis. We identified 5456 differential genes and obtained 26 ferroptosis-related differentially expressed genes. Through PPI, LASSO, and RFA, Hmox1 was identified as the only hub gene and its expression levels were verified using verification sets. In animal experiments, Hmox1 was verified as a key biomarker. GSEA of single genes revealed the seven most related pathways, and the ceRNAs network included 138 mRNAs and miRNAs. We predicted 11 related drugs and their three-dimensional structural maps. Thus, Hmox1 was identified as a key biomarker and regulator of ferroptosis in RIRI and its regulation of ferroptosis was closely related to immune infiltration.
摘要：
缺血再灌注损伤(IRI)在肾移植中是不可避免的,作为一个复杂的病理生理过程，它可以受到铁死亡和免疫炎症的极大影响。我们的研究旨在鉴定肾IRI（RIRI）的生物标志物，并阐明它们与免疫浸润的关系。在这项研究中,GSE148420数据库用作训练集来分析差异基因，并将其与铁凋亡相关基因重叠，以使用蛋白质-蛋白质相互作用（PPI）网络来识别集线器基因，最小绝对收缩和选择运算符(LASSO)，和随机森林算法(RFA)。我们在涉及大鼠单侧IRI和对侧肾切除术的验证集和动物实验中验证了hub基因和铁凋亡相关表型。根据hub基因对单基因进行基因集富集分析(GSEA),预测相关内源性RNA(ceRNA)和药物建立网络。最后,我们使用Cibersort进行了免疫学浸润分析，并进行了Spearman\的相关性分析。我们鉴定了5456个差异基因，并获得了26个与铁凋亡相关的差异表达基因。通过PPI，拉索,RFA,Hmox1被鉴定为唯一的hub基因，其表达水平使用验证集进行验证。在动物实验中,Hmox1被验证为关键生物标志物。单个基因的GSEA揭示了七种最相关的途径，CERNA网络包括138个mRNA和miRNA。我们预测了11种相关药物及其三维结构图。因此，Hmox1是RIRI中铁凋亡的关键生物标志物和调节因子，其对铁凋亡的调节与免疫浸润密切相关。
