通过生物信息学分析鉴定急性肾损伤中的铁蛋白沉积相关基因

Jianfeng Ye, Yun Cen, Man Li, Wanjie Gu, Xuehao Lu, Fengzhi Zhao, Bowen Shi, Jun Xu, Haiyan Yin
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摘要

急性肾损伤(AKI)是指肾功能在短时间内急剧下降,其特点是肾小球滤过率下降。铁变态反应影响各种肾脏疾病的发展。因此,寻找与高铁血症相关的基因对于了解 AKI 的发生和发展至关重要。 我们从 GSE53769 的 18 个样本(8 个急性肾损伤样本和 10 个非病理组织样本)和 GSE139061 的 48 个样本(39 个急性肾损伤样本和 9 个非病理组织样本)中获得了数据。我们从这两个数据集中获得了 AKI/对照样本的差异表达基因(DEGs),并将它们与已知的铁蛋白沉积相关基因(FRGs)交叉,从而获得了铁蛋白沉积相关 DEGs(FRDEGs)。我们对FRDEGs进行了GO注释、KEGG通路分析和GSEA分析,以了解其富集的生物学功能和通路。接着,我们构建了蛋白质-蛋白质相互作用(PPI)网络。 我们共获得了 312 个基因,这些基因在两个数据集中都有异常表达。在与已知的FRGs交叉后,得到了14个FRDEGs,即ACSF2、ADIPOR1、ARF6、ATF3、ATF6、DPEP1、FH、GLRX5、MIOX、NAP1L1、NDRG1、PPARA、SPHK1、YY1AP1。免疫浸润分析结果显示,14 个基因中的多个基因表达与免疫细胞浸润相关。 14个铁变态反应基因(ACSF2、ADIPOR1、ARF6、ATF3、ATF6、DPEP1、FH、GLRX5、MIOX、NAP1L1、NDRG1、PPARA、SPHK1、YY1AP1)参与了AKI的发生和发展,其中NDRG1可能是核心功能基因,而PPARA有望成为最有效的治疗靶基因。
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Identification of ferroptosis-related genes in acute kidney injury by bioinformatic analysis
Acute kidney injury (AKI) is a rapid decline in renal function characterized by a decrease in glomerular filtration rate in a short period. Ferroptosis affects the development of various kidney diseases. Therefore, searching for genes related to ferroptosis is crucial for understanding the occurrence and development of AKI. We obtained data from 18 samples (8 with acute kidney injury and 10 non-pathological tissue) in GSE53769 and 48 samples (39 with acute kidney injury and 9 non-pathological tissue) in GSE139061. We obtained differentially expressed genes (DEGs) of AKI/Control samples from both two datasets and intersected them with known ferroptosis-related genes (FRGs) to obtain ferroptosis-related DEGs (FRDEGs). GO annotation, KEGG pathway analysis, and GSEA analysis were conducted on the FRDEGs to understand their enriched biological functions and pathways. Next, we constructed the protein-protein interaction (PPI) network. A total of 312 genes were obtained, which were abnormally expressed in both two datasets. After intersecting with known FRGs, 14 FRDEGs were obtained, namely ACSF2, ADIPOR1, ARF6, ATF3, ATF6, DPEP1, FH, GLRX5, MIOX, NAP1L1, NDRG1, PPARA, SPHK1, YY1AP1. The results of the immune infiltration analysis showed that multiple gene expressions among 14 genes are correlated with immune cell infiltration. Fourteen ferroptosis genes (ACSF2, ADIPOR1, ARF6, ATF3, ATF6, DPEP1, FH, GLRX5, MIOX, NAP1L1, NDRG1, PPARA, SPHK1, YY1AP1) are involved in the occurrence and development of AKI, among which NDRG1 might be the core functional gene, and PPARA is expected to become the most effective therapeutic target gene.
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