Department of Pediatric Surgrey, Guizhou Provincial People's Hospital, Guiyang 550002, China.
Department of Pediatric Surgrey, Guizhou Provincial People's Hospital, Guiyang 550002, China.
Transpl Immunol. 2024 Aug;85:102082. doi: 10.1016/j.trim.2024.102082. Epub 2024 Jul 11.
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.
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.
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).
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.
硒蛋白水平的变化与肾移植急性排斥反应密切相关，硒蛋白对维持体内氧化还原平衡非常重要。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。
我们首先通过富集分析探讨了 25 种人体硒蛋白的潜在生物学功能，并利用 HPA 数据库阐明了肾组织中硒蛋白的表达水平；然后，我们使用“Logistic 回归分析”和“列线图模型”构建了诊断模型；校准曲线和 ROC 曲线用于评估诊断模型，临床决策曲线（DCA）用于评估硒蛋白变化对临床的诊断价值；单基因 GSEA 富集分析进一步探讨了硒蛋白的潜在调控机制；Cibersort 算法探讨免疫细胞浸润水平，并通过相关性分析阐明硒蛋白与免疫细胞的相关性；我们进一步评估了硒蛋白在肾移植 ABMR 和 TCMR 中的诊断价值。最后，我们通过构建大鼠肾移植急性排斥反应模型，使用转录组测序验证了肾组织中硒蛋白的表达水平。
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学功能密切相关（P<0.05）；HPA 数据库表明，总共 23 种硒蛋白可在肾组织中表达。我们使用这 23 种硒蛋白构建了诊断模型，校准曲线和 ROC 曲线均证明其变化水平对肾移植急性排斥反应具有良好的诊断价值，DCA 曲线证明了硒蛋白在临床决策中的作用；单基因 GSEA 富集分析表明，硒蛋白与免疫调节相关途径密切相关（P<0.05）；Cibersort 算法确定了 10 种在肾移植急性排斥反应过程中显著改变的免疫细胞浸润水平（P<0.05），而相关性分析表明硒蛋白与多种免疫细胞浸润相关；在 ABMR 和 TCMR 中，我们再次验证了硒蛋白变化对肾移植急性排斥反应的诊断价值。最后，我们在大鼠肾移植急性排斥反应模型中发现 9 种硒蛋白的表达水平有显著差异（P<0.05）。
肾组织中硒蛋白的变化对肾移植急性排斥反应具有良好的诊断价值，硒蛋白可能成为缓解肾移植急性排斥反应的潜在靶点。
