Identification of Subtypes and a Delayed Graft Function Predictive Signature Based on Ferroptosis in Renal Ischemia-Reperfusion Injury

• DOI: 10.3389/fcell.2022.800650
• Publication Date: 2022-02-08T08:14:06Z
• Authors: Xiangling Wei; Weiming Deng; Zhanwen Dong; Zhenwei Xie; Jinhua Zhang; Ruojiao Wang; Rui Zhang; Ning Na; Yu Zhou
• Keywords: Gene signature

Renal ischemia-reperfusion injury (IRI) is an inevitable process in kidney transplantation, leading to acute injury, delayed graft function (DGF), and even loss. Ferroptosis iron-dependent regulated cell death various diseases including IRI. We aimed identify subtypes of renal IRI construct a robust DGF predictive signature based on ferroptosis-related genes (FRGs). A consensus clustering analysis was applied ferroptosis-associated 203 samples the GSE43974 dataset. The FRG-associated constructed using Least Absolute Shrinkage Selection Operator (LASSO), its robustness further verified validation set GSE37838. present study revealed two patient clusters (pBECN1 pNF2 cluster) distinct expression patterns BECN1 NF2 gene clusters. Cluster pBECN1 metabolically active closely correlated with less DGF, while regarded as metabolic exhausted subtype higher incidence DGF. Additionally, six-gene (ATF3, SLC2A3, CXCL2, DDIT3, ZFP36) predict occurrence patients exhibited efficacy both training sets. High-risk tended have more infiltration dendritic cells, macrophages, T they had significantly enriched chemokine-related pathway, WNT/β-catenin signaling allograft rejection. Patients low risks were associated pathways such glutathione fatty acid metabolism pathways. In conclusion, stratification activities ferroptosis may help distinguish who respond therapeutics. Moreover, FRGs guide advanced strategies toward prevention early stage.