validation study of existing gene expression signatures for anti-tnf treatment in patients with rheumatoid arthritis验证现有的基因表达研究签名anti-tnf治疗类风湿性关节炎患者.pdfVIP

Validation Study of Existing Gene Expression Signatures for Anti-TNF Treatment in Patients with Rheumatoid Arthritis 1 2 2 3 4 Erik J. M. Toonen , Christian Gilissen , Barbara Franke , Wietske Kievit , Agnes M. Eijsbouts , Alfons A. 4 2 2 2 3 den Broeder , Simon V. van Reijmersdal , Joris A. Veltman , Hans Scheffer , Timothy R. D. J. Radstake , 3 3 2 Piet L. C. M. van Riel , Pilar Barrera , Marieke J. H. Coenen * 1 Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 2 Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 3 Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 4 Department of Rheumatology of the St Maartenskliniek, Nijmegen, The Netherlands Abstract So far, there are no means of identifying rheumatoid arthritis (RA) patients who will fail to respond to tumour necrosis factor blocking agents (anti-TNF), prior to treatment. We set out to validate eight previously reported gene expression signatures predicting therapy outcome. Genome-wide expression profiling using Affymetrix GeneChip Exon 1.0 ST arrays was performed on RNA isolated from whole blood of 42 RA patients starting treatment with infliximab or adalimumab. Clinical response according to EULAR criteria was determined at week 14 of therapy. Genes that have been reported to be associated with anti-TNF treatment were extracted from our dataset. K-means partition clusterin