Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Institute of Urology, Capital Medical University, Beijing, China.
BMC Med Genomics. 2023 Jan 19;16(1):11. doi: 10.1186/s12920-023-01440-y.
T cell-mediated rejection is an important factor affecting early transplant kidney survival. Ferroptosis has been shown to play a pathogenic role in a variety of diseases, which was not reported in TCMR. Here we developed a model for assessing activation of ferroptosis-related genes in TCMR to find a better screening method and explore the contribution of ferroptosis in TCMR.
We performed unsupervised consensus clustering according to expression of ferroptosis-related genes based on RNA-seq data from kidney transplant biopsies, and developed an assessment model characterized by ferroptosis gene expression through PCA, which was evaluated in multiple external datasets as well as blood and urine samples. Pathway enrichment and immune cell infiltration analysis were used to explore the possible targets and pathways involved in ferroptosis and TCMR.
A ferroptosis gene expression scoring model was established. The diagnostic specificity and sensitivity of TCMR in renal biopsy samples were both over 80%, AUC = 0.843, and AUC was around 0.8 in multi-dataset validation, and was also close to 0.7 in blood and urine samples, while in predicting of graft survival at 3 years, scoring model had a good prognostic effect as well. Pathway enrichment and PPI network speculated that TLR4, CD44, IFNG, etc. may be the key genes of ferroptosis in TCMR.
Ferroptosis scoring model could better diagnose TCMR and predict graft loss, and could be used as a potential screening method in blood and urine samples. We speculate that ferroptosis plays an important role in TCMR.
T 细胞介导的排斥反应是影响移植肾早期存活的重要因素。铁死亡在多种疾病中发挥着致病作用，但在 TCMR 中尚未有报道。在这里，我们建立了一个评估 TCMR 中与铁死亡相关基因激活的模型，以寻找更好的筛选方法，并探索铁死亡在 TCMR 中的作用。
我们根据肾移植活检的 RNA-seq 数据，根据铁死亡相关基因的表达进行无监督共识聚类，并通过 PCA 开发了一个以铁死亡基因表达为特征的评估模型，该模型在多个外部数据集以及血液和尿液样本中进行了评估。通路富集和免疫细胞浸润分析用于探索铁死亡和 TCMR 中涉及的可能靶点和通路。
建立了铁死亡基因表达评分模型。该模型在肾活检样本中诊断 TCMR 的特异性和敏感性均超过 80%，AUC=0.843，在多数据集验证中 AUC 约为 0.8，在血液和尿液样本中也接近 0.7，而在预测 3 年移植物存活率方面，评分模型也具有良好的预后效果。通路富集和 PPI 网络推测 TLR4、CD44、IFNG 等可能是 TCMR 中铁死亡的关键基因。
铁死亡评分模型可更好地诊断 TCMR 和预测移植物丢失，可作为血液和尿液样本中的潜在筛选方法。我们推测铁死亡在 TCMR 中发挥重要作用。
