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Status |
Public on Jun 15, 2019 |
Title |
WNT Pathway Signalling in Kidney Transplants with Microvascular Injury |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Kidney transplant recipients with biopsy-proven microvascular injury (MVI) have increased risk for allograft failure. MVI is often caused by antibody-mediated injury that is resistant to available treatments. Current diagnostic methods are also inadequate, with interobserver variability in traditional pathology reads, variable assessment of circulating donor-specific antibody between HLA laboratories, and peritubular capillary C4d staining. Molecular assessments of kidney biopsies can provide improved sensitivity for diagnosing MVI and other allograft pathology, while improving reproducibility and objectivity. Most molecular classifiers have been based on whole genome sequencing to develop diagnostic tests, but have provided limited therapeutic targets. In this study, we pursued a candidate gene approach to measure WNT pathway genes in residual clinical FFPE biopsies with and without MVI. We focused on the WNT pathway because of previous translational studies that implicated this pathway in chronic renal allograft injury as well as vascular injury in native chronic kidney disease.
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Overall design |
Case-control study of 95 residual FFPE biopsies with MVI (g+ptc score >= 2, n=50) or Stable (g+ptc score < 2 and no other major abnormalities, n=45). Biopsies were retrieved from a biorepository of over 500 kidney transplant biopsies. We compared expression of 180 WNT pathway genes and 30 custom skipe-in targets (derived from previous studies of endothelial injury in transplantation) between MVI and Stable groups, with correction for multiple comparisons using FDR < 5%.
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Contributor(s) |
Seifert ME, Mannon RB |
Citation(s) |
30916889 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
K23 DK101690 |
Novel Biomarkers of Angiogenesis and Vascular Injury in Chronic Rejection |
UNIVERSITY OF ALABAMA AT BIRMINGHAM |
Michael Edward Seifert |
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Submission date |
Jun 19, 2018 |
Last update date |
Sep 15, 2019 |
Contact name |
Michael Edward Seifert |
Organization name |
UAB School of Medicine
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Street address |
1600 7th Ave S Lowder 516
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City |
Birmingham |
State/province |
AL |
ZIP/Postal code |
35233-1711 |
Country |
USA |
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Platforms (1) |
GPL25197 |
Nanostring nCounter Vantage RNA WNT Pathways Panel (LBL-10251-03) |
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Samples (95)
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Relations |
BioProject |
PRJNA476707 |