背景:硒蛋白水平的变化之间似乎有密切的联系,这对维持体内的氧化还原稳态很重要,和肾移植的急性排斥反应。本研究旨在探讨肾组织硒蛋白变化特征对肾移植急性排斥反应的诊断价值。
方法:我们首先通过富集分析探索了25种硒蛋白在人体中的潜在生物学功能,并使用HPA数据库阐明了硒蛋白在肾脏组织中的表达水平;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,和临床决策曲线(DCA)评估硒蛋白变化对临床的诊断价值;单基因GSEA富集分析,进一步探讨硒蛋白的潜在调控机制;Cibersort算法探索免疫细胞浸润水平,并利用相关性分析阐明硒蛋白与免疫细胞的相关性;我们进一步评估硒蛋白在肾移植ABMR和TCMR中的诊断价值,分别。最后,我们利用转录组测序技术构建大鼠肾移植急性排斥反应模型,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等生物学功能密切相关,炎症,和免疫调节(P<0.05);HPA数据库表明,肾脏组织中可以表达总共23种硒蛋白。我们使用这23种硒蛋白构建了一个诊断模型,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有较好的诊断价值,和DCA曲线证明了硒蛋白在临床决策中的作用;单基因GSEA富集分析显示硒蛋白与免疫调节相关通路密切相关(P<0.05);Cibersort算法鉴定出10个在肾移植急性排斥反应中显著改变的免疫细胞浸润水平(P<0.05)。而相关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在肾移植急性排斥反应中的诊断价值。最后,我们发现9种硒蛋白在大鼠肾移植急性排斥反应模型中的表达水平差异有统计学意义(P<0.05)。
结论:肾组织中硒蛋白的变化对肾移植急性排斥反应有较好的诊断价值。硒蛋白可能是减轻肾移植急性排斥反应的潜在靶点。
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).
CONCLUSIONS: 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.