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探讨铁死亡相关基因作为急性肾损伤生物标志物的作用。

Exploring the role of ferroptosis-related genes as biomarkers in acute kidney injury.

机构信息

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Shaanxi, China.

Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China.

出版信息

PLoS One. 2024 Jul 23;19(7):e0307472. doi: 10.1371/journal.pone.0307472. eCollection 2024.

DOI:10.1371/journal.pone.0307472
PMID:39042632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11265698/
Abstract

INTRODUCTION

Acute kidney injury (AKI) is a severe condition with high morbidity and mortality. Innovative biomarkers and treatments are essential for improving patient outcomes. This study aims to investigate the role of ferroptosis-related genes (FRGs) in AKI for identifying potential biomarkers and therapeutic targets.

METHODS

We analyzed mRNA expression profiles from the Gene Expression Omnibus (GEO: GSE139061) dataset, comparing 36 AKI samples with 9 normal samples. Differentially expressed genes (DEGs) were identified using the R software package limma. Functional enrichment analyses were conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Key biomarkers were validated through area under the curve (AUC) values, and immune cell infiltration was analyzed using CIBERSORT.

RESULTS

We identified 78 differentially expressed FRGs, with 27 up-regulated and 51 down-regulated genes. Key signaling pathways included MAPK, ferroptosis, and p53. Five genes-NR4A1, GLRX5, USP35, AEBP2, and MDM4-were identified as potential biomarkers, each demonstrating AUC values greater than 0.800. Specifically, MDM4 showed significant potential by promoting the phosphorylation of p53 at Ser46, enhancing mitochondrial apoptotic activity. Immune analysis revealed a significant elevation of M0 macrophages in AKI samples compared to normal samples (P < 0.01).

CONCLUSION

Our findings highlight the critical role of ferroptosis-related genes in AKI, identifying NR4A1, GLRX5, USP35, AEBP2, and MDM4 as key biomarkers with high diagnostic potential. These results provide novel insights into the molecular mechanisms of AKI.

摘要

简介

急性肾损伤（AKI）是一种发病率和死亡率均较高的严重疾病。创新的生物标志物和治疗方法对于改善患者预后至关重要。本研究旨在探讨铁死亡相关基因（FRG）在 AKI 中的作用，以寻找潜在的生物标志物和治疗靶点。

方法

我们分析了基因表达综合数据库（GEO：GSE139061）数据集的 mRNA 表达谱，比较了 36 例 AKI 样本和 9 例正常样本。使用 R 软件包 limma 识别差异表达基因（DEG）。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）途径进行功能富集分析。通过曲线下面积（AUC）值验证关键生物标志物，并使用 CIBERSORT 分析免疫细胞浸润。

结果

我们鉴定出 78 个差异表达的 FRG，其中 27 个上调，51 个下调。关键信号通路包括 MAPK、铁死亡和 p53。NR4A1、GLRX5、USP35、AEBP2 和 MDM4 这 5 个基因被鉴定为潜在的生物标志物，每个基因的 AUC 值均大于 0.800。特别是 MDM4 通过促进 p53 在 Ser46 处的磷酸化，增强线粒体凋亡活性，显示出显著的潜在作用。免疫分析显示 AKI 样本中的 M0 巨噬细胞明显高于正常样本（P<0.01）。

结论

我们的研究结果强调了铁死亡相关基因在 AKI 中的关键作用，鉴定出 NR4A1、GLRX5、USP35、AEBP2 和 MDM4 作为具有高诊断潜力的关键生物标志物。这些结果为 AKI 的分子机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7e2/11265698/e522588a3cb8/pone.0307472.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7e2/11265698/147b8117c152/pone.0307472.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7e2/11265698/e522588a3cb8/pone.0307472.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7e2/11265698/0521a2c46047/pone.0307472.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7e2/11265698/2a0ee54efa75/pone.0307472.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7e2/11265698/c2722ae607f1/pone.0307472.g003.jpg
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