Identification of differentially expressed genes from kidney transplant recipients in Northern Ireland

Belfast City Hospital is a kidney transplantation centre with the highest living donor transplant rate per million population in Europe. Kidney transplantation is a gold standard treatment for end stage renal disease, however there are significant complications associated with immunosuppression, such as an increased risk of diabetes and cancer. To date there have been limited transcriptomic analyses of patients following kidney transplantation. We aimed to identify differentially expressed genes (DEGs) and pathways associated with kidney disease and those that may be indicative of complications associated with kidney transplantation.

Targeted RNA sequencing was conducted using the Ion AmpliSeq™ Human Gene Expression Core Panel from peripheral blood mononuclear cells, to identify DEGs in kidney transplant recipients (n=37, median age = 54 yrs) compared to individuals with no evidence of renal disease (n=21 controls, median age = 56 yrs). In the kidney transplant group, 15 had a previous cancer diagnoses, one participant had unknown cancer status and three participants had new onset diabetes after transplantation (NODAT).

Analyses comparing transplant recipients to controls, identified 1089 significant DEGs with a 2 fold +/- change in expression (P ≤ 0.1x10-8). The pancreatic cancer pathway was significantly enriched with identification of six significant DEG in this pathway previously associated with several cancer types and/or diabetes (RALA, JAK1, PIK3CA, MAPK8, JNK, SMAD2). Outside of the pancreatic cancer pathway, BAP1, a gene previously associated with renal tumorigenesis, was identified to have significantly increased expression (p=7.3x10-13) in kidney transplant recipients compared to controls. Gene ontology analysis identified enrichment in metabolic process, cellular process and biogenesis.

Our analyses have illustrated a significant enrichment in the pancreatic cancer pathway, as well as genes associated with several non-pancreatic cancers and diabetes, in kidney transplant patients approximately 20 years post-transplantation. RNA-seq and additional multi-omic analysis, in a larger case-control study, will help determine if exploration of a transplant recipient’s molecular profile can predict risk of developing certain cancers and NODAT following transplant.