Molecular classifiers for acute kidney transplant rejection in peripheral blood by whole genome gene expression profiling
| Autor: | Stuart M. Flechner, Laurence Chan, Ryan Thompson, Terri Gelbart, Wen Lin, Steven R. Head, Jonathan S. Fisher, Elizabeth H Robison, A. Williams, Tony S. Mondala, Alexander C. Wiseman, Thomas Whisenant, Lillian W. Gaber, John J. Friedewald, Raymond L. Heilman, Stephen Horvath, Sunil M. Kurian, Michael Abecassis, Randolph Schaffer, Peter Langfelder, Robert Mendez, Daniel R. Salomon, Daniel Campbell, H. Shidban, Christopher L. Marsh |
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| Rok vydání: | 2013 |
| Předmět: |
Oncology
Adult Graft Rejection Male Pathology medicine.medical_specialty Sensitivity and Specificity Article Postoperative Complications Predictive Value of Tests Internal medicine medicine Immunology and Allergy Humans Pharmacology (medical) Prospective Studies Prospective cohort study False Negative Reactions Kidney transplantation Oligonucleotide Array Sequence Analysis Transplantation business.industry Gene Expression Profiling Confounding Area under the curve Middle Aged medicine.disease Prognosis Kidney Transplantation Gene expression profiling Predictive value of tests Area Under Curve Kidney Failure Chronic Female DNA microarray business Biomarkers Follow-Up Studies |
| Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 14(5) |
| ISSN: | 1600-6143 |
| Popis: | There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction. |
| Databáze: | OpenAIRE |
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