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.
|Accepted - 23 Jul 2019
|The American Society of Human Genetics - Houston, United States
Duration: 15 Oct 2019 → 19 Oct 2019
|The American Society of Human Genetics
|15/10/2019 → 19/10/2019
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Kerr, K., Jul 2021
Student thesis: Doctoral Thesis › Doctor of Philosophy