Uncover diagnostic immunity/hypoxia/ferroptosis/epithelial mesenchymal transformation-related CCR5, CD86, CD8A, ITGAM, and PTPRC in kidney transplantation patients with allograft rejection

• Published in: Renal failure Vol. 44; no. 1; pp. 1860 - 1875
• Main Authors: He, Long, Wang, Boqian, Wang, Xueyi, Liu, Yuewen, Song, Xing, Zhang, Yijian, Li, Xin, Yang, Hongwei
• Format: Journal Article
• Language: English
• Published: New York Taylor & Francis 31.12.2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: allograft rejection; CCR5 protein; CD86 antigen; Clarithromycin; Clinical Study; Correlation analysis; epithelial mesenchymal transformation; Erythropoietin; Ferroptosis; Gene expression; Genetic transformation; Graft rejection; Hypoxia; Immunity; Immunosuppressive agents; Kidney transplantation; Kidney transplants; Mesenchyme; Microenvironments; Prednisone; Therapeutic targets
• ISSN: 0886-022X; 1525-6049
• DOI: 10.1080/0886022X.2022.2141648

The aim of this study was to identify predictive immunity/hypoxia/ferroptosis/epithelial mesenchymal transformation (EMT)-related biomarkers, pathways and new drugs in allograft rejection in kidney transplant patients. First, gene expression data were downloaded followed by identification of differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) analysis. Second, diagnostic model was construction based on key genes, followed by correlation analysis between immune/hypoxia/ferroptosis/EMT and key diagnostic genes. Finally, drug prediction of diagnostic key genes was carried out. Five diagnostic genes were further identified, including CCR5, CD86, CD8A, ITGAM, and PTPRC, which were positively correlated with allograft rejection after the kidney transplant. Highly infiltrated immune cells, highly expression of hypoxia-related genes and activated status of EMT were significantly positively correlated with five diagnostic genes. Interestingly, suppressors of ferroptosis (SOFs) and drivers of ferroptosis (DOFs) showed a complex regulatory relationship between ferroptosis and five diagnostic genes. CD86, CCR5, and ITGAM were respectively drug target of ABATACEPT, MARAVIROC, and CLARITHROMYCIN. PTPRC was drug target of both PREDNISONE and EPOETIN BETA. In conclusion, the study could be useful in understanding changes in the microenvironment within transplantation, which may promote or sustain the development of allograft rejection after kidney transplantation.