Validation of Biomarkers in Gene Expression Datasets of Inflammatory Bowel Disease: IL13RA2, PTGS2 and WNT5A as Predictors of Responsiveness to Infliximab Therapy
- *Corresponding Author:
- Barna Vásárhelyi
Department of Laboratory Medicine
Semmelweis University Nagyvárad tér 4.
1089 Budapest, Hungary
Fax: 0036-1-2100278 Ext. 56492
E-mail: [email protected]
Received Date: July 24, 2014; Accepted Date: August 28, 2014; Published Date: September 01, 2014
Citation: Gyorffy A, Kormos M, Bartha L, Szabó A, Gyorffy B, et al. (2014) Validation of Biomarkers in Gene Expression Datasets of Inflammatory Bowel Disease: IL13RA2, PTGS2 and WNT5A as Predictors of Responsiveness to Infliximab Therapy. J Proteomics Bioinform 7:272-277. doi: 10.4172/jpb.1000329
Copyright: © 2014 Gyorffy A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: Some patients with inflammatory bowel disease (IBD) do not respond to infliximab (IFX) therapy. Gene expression studies revealed genes that may help to predict non-responding IBD patients. Our purpose was to validate the discriminating power of published genes.
Methods: Microarray datasets of IBD patients responding or non-responding to IFX were downloaded from GEO database (‘transcriptomic arm’). Published genes discriminating responding and non-responding patients were identified in PubMed (‘biomarker arm’). Using ROC-analysis, the discriminating performance of genes in ‘biomarker arm’ were re-tested in each datasets of ‘transcriptomic arm’. We also performed an independent analysis of colon biopsy datasets to identify novel discriminating genes.
Results: The transcriptomic arm of four GEO datasets (3 and 1 from colon biopsies and blood cells, respectively) included 99 patients (of those, 59 and 40 were IFX responder and non-responder, respectively). Of the 65 candidate genes reported in biopsy specimens 25 genes discriminated significantly (p<0.05) infliximab responders and nonresponders in the three biopsy datasets consistently. Of the 39 candidate genes reported in peripheral blood 9 genes provided significant discrimination after re-testing. Independent analysis of three biopsy datasets identified the top five genes. Three genes (IL13RA2, PTGS2 and WNT5A) were highly effective discriminator in each analysis.
Conclusion: This analysis identified IL13RA2, PTGS2 and WNT5A, three genes in colonic tissues of IBD patients as suitable to discrimination between patients responding and non-responding to IFX therapy. These genes encode proteins implicated in intestinal pathology; the high expression in non-responding patients may indicate important targets in IBD therapy.