Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis.

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 expressi...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Erik J M Toonen, Christian Gilissen, Barbara Franke, Wietske Kievit, Agnes M Eijsbouts, Alfons A den Broeder, Simon V van Reijmersdal, Joris A Veltman, Hans Scheffer, Timothy R D J Radstake, Piet L C M van Riel, Pilar Barrera, Marieke J H Coenen
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
Materias:
R
Q
Acceso en línea:https://doaj.org/article/f82ca101767b4a1f92e2ffe26a4e189b
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:f82ca101767b4a1f92e2ffe26a4e189b
record_format dspace
spelling oai:doaj.org-article:f82ca101767b4a1f92e2ffe26a4e189b2021-11-18T07:24:37ZValidation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis.1932-620310.1371/journal.pone.0033199https://doaj.org/article/f82ca101767b4a1f92e2ffe26a4e189b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22457743/?tool=EBIhttps://doaj.org/toc/1932-6203So 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 clustering was performed to assess the predictive value of the gene-sets. We performed a hypothesis-driven analysis of the dataset using eight existing gene sets predictive of anti-TNF treatment outcome. The set that performed best reached a sensitivity of 71% and a specificity of 61%, for classifying the patients in the current study. We successfully validated one of eight previously reported predictive expression profile. This replicated expression signature is a good starting point for developing a prediction model for anti-TNF treatment outcome that can be used in a daily clinical setting. Our results confirm that gene expression profiling prior to treatment is a useful tool to predict anti-TNF (non) response.Erik J M ToonenChristian GilissenBarbara FrankeWietske KievitAgnes M EijsboutsAlfons A den BroederSimon V van ReijmersdalJoris A VeltmanHans SchefferTimothy R D J RadstakePiet L C M van RielPilar BarreraMarieke J H CoenenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e33199 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Erik J M Toonen
Christian Gilissen
Barbara Franke
Wietske Kievit
Agnes M Eijsbouts
Alfons A den Broeder
Simon V van Reijmersdal
Joris A Veltman
Hans Scheffer
Timothy R D J Radstake
Piet L C M van Riel
Pilar Barrera
Marieke J H Coenen
Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis.
description 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 clustering was performed to assess the predictive value of the gene-sets. We performed a hypothesis-driven analysis of the dataset using eight existing gene sets predictive of anti-TNF treatment outcome. The set that performed best reached a sensitivity of 71% and a specificity of 61%, for classifying the patients in the current study. We successfully validated one of eight previously reported predictive expression profile. This replicated expression signature is a good starting point for developing a prediction model for anti-TNF treatment outcome that can be used in a daily clinical setting. Our results confirm that gene expression profiling prior to treatment is a useful tool to predict anti-TNF (non) response.
format article
author Erik J M Toonen
Christian Gilissen
Barbara Franke
Wietske Kievit
Agnes M Eijsbouts
Alfons A den Broeder
Simon V van Reijmersdal
Joris A Veltman
Hans Scheffer
Timothy R D J Radstake
Piet L C M van Riel
Pilar Barrera
Marieke J H Coenen
author_facet Erik J M Toonen
Christian Gilissen
Barbara Franke
Wietske Kievit
Agnes M Eijsbouts
Alfons A den Broeder
Simon V van Reijmersdal
Joris A Veltman
Hans Scheffer
Timothy R D J Radstake
Piet L C M van Riel
Pilar Barrera
Marieke J H Coenen
author_sort Erik J M Toonen
title Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis.
title_short Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis.
title_full Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis.
title_fullStr Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis.
title_full_unstemmed Validation study of existing gene expression signatures for anti-TNF treatment in patients with rheumatoid arthritis.
title_sort validation study of existing gene expression signatures for anti-tnf treatment in patients with rheumatoid arthritis.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/f82ca101767b4a1f92e2ffe26a4e189b
work_keys_str_mv AT erikjmtoonen validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT christiangilissen validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT barbarafranke validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT wietskekievit validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT agnesmeijsbouts validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT alfonsadenbroeder validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT simonvvanreijmersdal validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT jorisaveltman validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT hansscheffer validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT timothyrdjradstake validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT pietlcmvanriel validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT pilarbarrera validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
AT mariekejhcoenen validationstudyofexistinggeneexpressionsignaturesforantitnftreatmentinpatientswithrheumatoidarthritis
_version_ 1718423510975512576