Diagnostic value of selenoprotein changes in renal tissues for acute rejection of kidney transplantation as revealed by transcriptomics

IF 1.6 4区 医学 Q4 IMMUNOLOGY Transplant immunology Pub Date : 2024-07-11 DOI:10.1016/j.trim.2024.102082
Xingyu Pan , Rong Zhu , Jinpu Peng, Hongyu Tang, Nini An, Jun Pei
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Abstract

Background

There seems to be a close link between the changing levels of selenoproteins, which are important for maintaining redox homeostasis in the body, and acute rejection of kidney transplants. The aim of this study was to explore the diagnostic value of selenoprotein change characteristics in renal tissues for acute rejection of kidney transplantation.

Methods

We first explored the potential biological functions of 25 selenoproteins in the human body by enrichment analysis and used the HPA database to clarify the expression levels of selenoproteins in kidney tissues; We then constructed a diagnostic model using “Logistic regression analysis” and “Nomogram model”; Calibration curves and ROC curves were used to evaluate the diagnostic models, and clinical decision curves (DCA) were used to assess the diagnostic value of selenoprotein changes to the clinic; Single-gene GSEA enrichment analysis to further explore the potential regulatory mechanisms of selenoproteins; The Cibersort algorithm explores the level of immune cell infiltration and uses correlation analysis to clarify the correlation between selenoproteins and immune cells; We further assessed the diagnostic value of selenoproteins in kidney transplantation ABMR and TCMR, respectively. Finally, we validated the expression level of selenoproteins in kidney tissues by constructing a rat model of acute rejection of kidney transplantation using transcriptome sequencing.

Results

Our enrichment analysis revealed that selenoproteins are mainly closely associated with biological functions such as oxidative stress, inflammation, and immune regulation (P<0.05); The HPA database suggests that a total of 23 selenoproteins can be expressed in kidney tissue. We constructed a diagnostic model using these 23 selenoproteins, and both calibration curves and ROC curves proved that their change levels have good diagnostic value for acute rejection of kidney transplantation, and DCA curves proved the role of selenoproteins in clinical decision-making; Single-gene GSEA enrichment analysis revealed that selenoproteins are closely associated with immune regulation-related pathways (P<0.05); The Cibersort algorithm identified 10 immune cell infiltration levels that were significantly altered during acute rejection of kidney transplantation (P<0.05), while correlation analyses indicated that selenoproteins correlate with multiple immune cell infiltrations; In ABMR and TCMR, we again verified the diagnostic value of selenoprotein changes in acute rejection of kidney transplantation. Finally, we found significant differences in the expression levels of nine selenoproteins in a rat model of acute rejection of kidney transplantation (P<0.05).

Conclusion

Changes in selenoproteins in renal tissues have good diagnostic value for acute rejection of kidneyl transplantation, and selenoproteins may be able to be a potential target for alleviating acute rejection of kidney transplantation.

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转录组学揭示的肾组织硒蛋白变化对肾移植急性排斥反应的诊断价值。
背景:硒蛋白是维持体内氧化还原平衡的重要物质,硒蛋白水平的变化与肾移植急性排斥反应之间似乎存在密切联系。本研究旨在探讨肾组织中硒蛋白变化特征对肾移植急性排斥反应的诊断价值:方法:首先通过富集分析探讨25种硒蛋白在人体内的潜在生物学功能,并利用HPA数据库明确硒蛋白在肾脏组织中的表达水平;然后利用 "逻辑回归分析 "和 "野图模型 "构建诊断模型;利用校正曲线和ROC曲线评估诊断模型,并利用临床决策曲线(DCA)评估硒蛋白变化对临床的诊断价值;单基因GSEA富集分析进一步探索硒蛋白的潜在调控机制;Cibersort算法探索免疫细胞浸润水平,并利用相关性分析明确硒蛋白与免疫细胞的相关性;我们分别进一步评估了硒蛋白在肾移植ABMR和TCMR中的诊断价值。最后,我们利用转录组测序技术构建了肾移植急性排斥反应大鼠模型,验证了硒蛋白在肾组织中的表达水平:结果:我们的富集分析表明,硒蛋白主要与氧化应激、炎症和免疫调节等生物功能密切相关(PC结论:硒蛋白在肾脏组织中的表达变化可能与肾脏功能有关:肾组织中硒蛋白的变化对肾移植急性排斥反应有很好的诊断价值,硒蛋白可能成为缓解肾移植急性排斥反应的潜在靶点。
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来源期刊
Transplant immunology
Transplant immunology 医学-免疫学
CiteScore
2.10
自引率
13.30%
发文量
198
审稿时长
48 days
期刊介绍: Transplant Immunology will publish up-to-date information on all aspects of the broad field it encompasses. The journal will be directed at (basic) scientists, tissue typers, transplant physicians and surgeons, and research and data on all immunological aspects of organ-, tissue- and (haematopoietic) stem cell transplantation are of potential interest to the readers of Transplant Immunology. Original papers, Review articles and Hypotheses will be considered for publication and submitted manuscripts will be rapidly peer-reviewed and published. They will be judged on the basis of scientific merit, originality, timeliness and quality.
期刊最新文献
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