Comprehensive analysis of cuproptosis-related genes in immune infiltration and development of a novel diagnostic model for acute kidney injury.

IF 3 3区医学 Q1 UROLOGY & NEPHROLOGY Renal Failure Pub Date : 2024-12-01 Epub Date: 2024-03-27 DOI:10.1080/0886022X.2024.2325035

Yajing Li, Yingxue Ding

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Abstract

Background: Acute kidney injury (AKI) represents a diverse range of conditions characterized by high incidence and mortality rates, and it is mainly associated with immune-mediated mechanisms and mitochondrial metabolism dysfunction. Cuproptosis, a recently identified form of programmed cell death dependent on copper, is closely linked to mitochondrial respiration and contributes to various diseases. Our study aimed to investigate the involvement of cuproptosis-related genes (CRGs) in AKI.

Methods: Identification of CRGs was conducted using differential expression analysis, and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using human sequencing profiles. Utilizing CIBERSORT algorithm, receiver operating characteristic (ROC) curve analysis, nomogram development, and decision curve analysis (DCA), the association among immune scores, CRGs, and the diagnostic value of these genes was explored.

Results: Notably, six CRGs (FDX1, DLD, DLAT, DBT, PDHA1, and ATP7A) were identified as significant differentiators between AKI and non-AKI groups. The ROC curve, based on these six genes, demonstrated an AUC value of 0.917, which was further validated using an additional dataset with an AUC value of 0.902. Nomogram and DCA further confirmed the accuracy of the model in predicting the risk of AKI.

Conclusion: This study elucidated the role of cuproptosis in AKI and revealed the association between CRGs and infiltrated immune cells through comprehensive bioinformatic techniques. The six-gene cuproptosis-related signature exhibited remarkable predictive efficiency for AKI.

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全面分析杯突相关基因在免疫浸润中的作用，建立急性肾损伤的新型诊断模型。

背景：急性肾损伤（AKI）是一种以高发病率和高死亡率为特征的多种疾病，主要与免疫介导机制和线粒体代谢功能障碍有关。铜中毒是最近发现的一种依赖于铜的程序性细胞死亡形式，与线粒体呼吸密切相关，并导致多种疾病。我们的研究旨在探讨杯突相关基因（CRGs）参与 AKI 的情况：方法：利用差异表达分析鉴定杯突相关基因，随后利用人类测序图谱进行基因本体（GO）和京都基因组百科全书（KEGG）通路富集分析。利用CIBERSORT算法、接收者操作特征曲线（ROC）分析、提名图开发和决策曲线分析（DCA），探讨了免疫评分、CRGs和这些基因的诊断价值之间的关联：结果：值得注意的是，有六个 CRG（FDX1、DLD、DLAT、DBT、PDHA1 和 ATP7A）被认为是区分 AKI 和非 AKI 组的重要因素。根据这六个基因绘制的 ROC 曲线显示，AUC 值为 0.917，通过使用额外的数据集进一步验证，AUC 值为 0.902。提名图和 DCA 进一步证实了该模型在预测 AKI 风险方面的准确性：这项研究阐明了杯突症在 AKI 中的作用，并通过综合生物信息学技术揭示了 CRGs 与浸润免疫细胞之间的关联。六基因杯突相关特征对 AKI 具有显著的预测效率。

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来源期刊

Renal Failure 医学-泌尿学与肾脏学

CiteScore

3.90

自引率

13.30%

发文量

374

审稿时长

1 months

期刊介绍： Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.