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Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis

(2009) GUT. 58(12). p.1612-1619
Author
Organization
Abstract
Background and aims: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor alpha (anti-TNF alpha) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis. Methods: Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. Results: For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity. Conclusion: Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-) response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis.
Keywords
INFLAMMATION, CELLS, OSTEOPROTEGERIN, EXPRESSION, RECEPTOR, PATHOGENESIS, INDUCTION, DISCOVERY, DIAGNOSIS

Citation

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MLA
Arijs, I., et al. “Mucosal Gene Signatures to Predict Response to Infliximab in Patients with Ulcerative Colitis.” GUT, vol. 58, no. 12, 2009, pp. 1612–19.
APA
Arijs, I., Li, K., Toedter, G., Quintens, R., Van Lommel, L., Van Steen, K., … Rutgeerts, P. (2009). Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis. GUT, 58(12), 1612–1619.
Chicago author-date
Arijs, I, K Li, G Toedter, R Quintens, L Van Lommel, Kristel Van Steen, P Leemans, et al. 2009. “Mucosal Gene Signatures to Predict Response to Infliximab in Patients with Ulcerative Colitis.” GUT 58 (12): 1612–19.
Chicago author-date (all authors)
Arijs, I, K Li, G Toedter, R Quintens, L Van Lommel, Kristel Van Steen, P Leemans, G De Hertogh, K Lemaire, M Ferrante, F Schnitzler, L Thorrez, K Ma, XYR Song, C Marano, G Van Assche, S Vermeire, K Geboes, F Schuit, F Baribaud, and P Rutgeerts. 2009. “Mucosal Gene Signatures to Predict Response to Infliximab in Patients with Ulcerative Colitis.” GUT 58 (12): 1612–1619.
Vancouver
1.
Arijs I, Li K, Toedter G, Quintens R, Van Lommel L, Van Steen K, et al. Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis. GUT. 2009;58(12):1612–9.
IEEE
[1]
I. Arijs et al., “Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis,” GUT, vol. 58, no. 12, pp. 1612–1619, 2009.
@article{5907038,
  abstract     = {Background and aims: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor alpha (anti-TNF alpha) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis. 
Methods: Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. 
Results: For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity. 
Conclusion: Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-) response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis.},
  author       = {Arijs, I and Li, K and Toedter, G and Quintens, R and Van Lommel, L and Van Steen, Kristel and Leemans, P and De Hertogh, G and Lemaire, K and Ferrante, M and Schnitzler, F and Thorrez, L and Ma, K and Song, XYR and Marano, C and Van Assche, G and Vermeire, S and Geboes, K and Schuit, F and Baribaud, F and Rutgeerts, P},
  issn         = {0017-5749},
  journal      = {GUT},
  keywords     = {INFLAMMATION,CELLS,OSTEOPROTEGERIN,EXPRESSION,RECEPTOR,PATHOGENESIS,INDUCTION,DISCOVERY,DIAGNOSIS},
  language     = {eng},
  number       = {12},
  pages        = {1612--1619},
  title        = {Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis},
  url          = {http://dx.doi.org/10.1136/gut.2009.178665},
  volume       = {58},
  year         = {2009},
}

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