Dataset: Three non-invasive protein biomarkers for solid-organ transplant rejection found through integrative genomics

We integrated three transplant rejection microarray studies examining gene expression in samples from pediatric renal, adult renal, and adult heart transplants. We performed one study ourselves and retrieved two others from the NCBI Gene Expression Omnibus (GEO)(GSE4470 and GSE1563). We identified 45 genes that were upregulated in common in acute rejection. Half were involved in one immune-related pathway. Among ten proteins we tested by serum ELISA, three successfully distinguished acute rejection from stable transplants. These were CXCL9, PECAM1, and CD44, with areas under the receiver operating characteristic curves of 0.844, 0.802, and 0.738, respectively. Immunohistochemistry showed that the PECAM1 protein was increased in acute rejection in renal, liver and heart transplants versus normal tissues. Our results show that integrating publicly-available gene expression data sets is a fast, powerful, and cost-effective way to identify serum-detectable diagnostic biomarkers. For new microarray experiments, we collected 18 acute rejection (AR) and 18 stable (STA) biopsy samples from pediatric renal allograft recipients at Stanford University. Written informed consent was obtained from all the subjects. The study was approved by the Stanford University Institutional Review Board. Nucleic acids from the samples were hybridized to Affymetrix U133 Plus 2.0 microarrays. AR samples were obtained at the time of a biopsy-proven acute rejection episode according to the Banff classification (IA, IIA, IIB). Prior to including the samples in this study, the diagnosis of acute rejection was confirmed by a pathologist. STA samples were obtained from patients with stable graft function during regular post-transplantation follow-up protocol biopsies. All three data sets (pediatric renal, adult renal, and adult heart) were normalized by the quantile-quantile method using dChip software. Ten proteins in serum were measured by using commercial ELISA kits.

Species:

human

Samples:

36

Source:

E-GEOD-14328

PubMed:

20150539

Updated:

Dec.12, 2014

Registered:

Sep.11, 2014