Gene expression profiles for predicting antibody‑mediated kidney allograft rejection: Analysis of GEO datasets

Abstract

Antibody‑mediated rejections (AMRs) are one of the most challenging complications that result in the deterioration of renal allograft function and graft loss in a large majority of cases. The purpose of the present study was to characterize a meta‑signature of differentially expressed RNAs associated with AMR in cases of kidney transplantation. Gene Expression Omnibus (GEO) dataset searches up to September 11, 2017, using Medical Subject Heading terms and keywords associated with kidney transplantation, AMR and mRNA arrays were downloaded from the GEO dataset. Using a computational analysis, a meta‑signature was determined that characterized the significant intersection of differentially expressed genes (DEGs). Gene‑set and network analyses were also performed to identify gene sets and sub‑networks associated with the AMR‑related traits. A statistically significant mRNA meta‑signature of upregulated and downregulated gene expression levels that were significantly associated with AMR was identified. C‑X‑C motif chemokine ligand 10 (CXCL10), CXCL9 and guanylate binding protein 1 were the most significantly associated with AMR. DEGs were efficiently identified and were found to be able to predict the occurrence of AMR according to a meta‑analysis approach from publicly available datasets. These methods and results can be applied for a more accurate diagnosis of AMR in transplant cases.

Identification of Multiple Hub Genes in Acute Kidney Injury after Kidney Transplantation by Bioinformatics Analysis

“…PIK3AP1 regulates the inflammatory signal transduction and Toll-like receptor signal transduction. Upregulated expressed genes of PIK3AP1 were associated with antibody-mediated rejection in kidney transplantation in the analysis of GEO datasets [ 18 ].…”

Computational Prediction of Biomarkers, Pathways, and New Target Drugs in the Pathogenesis of Immune-Based Diseases Regarding Kidney Transplantation Rejection

“…Kim et al. ( 25 ) performed a meta-analysis where they obtained that CXCL10, CXCL9, and GBP1 were the most over-expressed genes with AMR. Unlike the study carried out by Kim et al.…”

“…In the context of KT, few studies have focused on studying the specific expression patterns of AMR. Kim et al (25) performed a meta-analysis where they obtained that CXCL10, CXCL9, and GBP1 were the most over-expressed genes with AMR. Unlike the study carried out by Kim et al (25), our work has focused exclusively on samples derived from biopsies, excluding those obtained from blood and PBMCs, intending to increase the homogeneity of the study, since the expression profiles in blood and graft may differ, leading to discrepancies between studies, making them difficult to compare.…”

“…Kim et al (25) performed a meta-analysis where they obtained that CXCL10, CXCL9, and GBP1 were the most over-expressed genes with AMR. Unlike the study carried out by Kim et al (25), our work has focused exclusively on samples derived from biopsies, excluding those obtained from blood and PBMCs, intending to increase the homogeneity of the study, since the expression profiles in blood and graft may differ, leading to discrepancies between studies, making them difficult to compare.…”

Comparison of blood pressure values and expression of genes associated with hypertension in children before and after hematopoietic cell transplantation

“…These were host cells in patients before HCT, and graft cells in patients after HCT. The differences in gene expression in host and graft cells are known and are subject of research focused on transplant rejection and tolerance [26][27][28][29][30] . The effects of microenvironment on gene expression are also implicated with respect to tumor angiogenesis 31 .…”