TY - JOUR
T1 - Predicting risk of postoperative disease recurrence in Crohn's disease
T2 - Patients with indolent Crohn's disease have distinct whole transcriptome profiles at the time of first surgery
AU - Cushing, Kelly C.
AU - McLean, Richard
AU - McDonald, Keely G.
AU - Gustafsson, Jenny K.
AU - Knoop, Kathryn A.
AU - Kulkarni, Devesha H.
AU - Sartor, R. Balfour
AU - Newberry, Rodney D.
N1 - Funding Information:
From the *Department of Internal Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA; †Department of Medicine, Microbiology and Immunology, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina, USA Conflicts of interest: RM and KM have no conflicts to declare. KC has no conflicts of interest to declare but is supported by T32DK007130 and UL1TR000448 NIH grants. JG has no conflicts of interest to declare but is supported by the Swedish Research Council no. 537-2014-366. KK has no conflicts of interest to declare but is supported by National Institutes of Health (DK109006). DK has no conflicts of interest to declare but is supported by a research fellowship award from the Crohn’s and Colitis Foundation of America (348359).
Funding Information:
Supported by: Research reported in this publication was supported by the the Sinai Helmsley Alliance for Research Excellence (SHARE) consortium, National Institutes of Health grants T32DK007130, P30DK052574, R01DK097317, PO1DK094779 and the Washington University Institute of Clinical and Translational Sciences grant UL1TR000448 from the National Center for Advancing Translational Sciences (NCATS). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.
Publisher Copyright:
© 2018 Crohn's and Colitis Foundation. Published by Oxford University Press. All rights reserved.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Background Assessing risk of Crohn's disease (CD) recurrence following ileocolic resection (ICR) is necessary to optimize medical management and prevent long-term complications. This study aimed to identify noninvasive markers that could predict postoperative disease activity. Methods Inclusion criteria were a diagnosis of CD, first ICR, interval colonoscopy, and whole transcriptome array meeting quality control standards. Demographic and clinical data were obtained from the electronic medical record. RNA extraction and human transcriptome microarray were performed on noninflamed ileal margins from operative specimens. Clinical data and random forest were analyzed in R. Principal components analysis, hierarchical clustering, and pathway enrichment were performed in Partek. Results Sixty-five patients completed the study, and 5 were excluded from analysis due to extreme variability on whole transcriptome analysis. Unsupervised hierarchical clustering revealed that patients with an i0 Rutgeerts score generally segregated from all others. In anti-TNF-naïve patients, unsupervised hierarchical clustering revealed complete segregation of patients with an i0 score. Reduced escalation in therapy and continued mucosal remission, consistent with indolent disease, were seen in the 4 years following surgery. Random forest identified 30 transcripts differentiating i0 patients from the other groups. Pathway enrichment highlighted toll-like receptor, NOD-like receptor, and TNF signaling. This transcriptome signature did not identify i0 anti-TNF-exposed patients. However, anti-TNF-exposed patients with indolent postoperative courses were found to have a transcriptome signature distinct from those with aggressive disease. Conclusions Anti-TNF-naïve and-exposed patients have unique expression profiles at the time of surgery, which may offer predictive value in assessing the risk of nonrecurrence.
AB - Background Assessing risk of Crohn's disease (CD) recurrence following ileocolic resection (ICR) is necessary to optimize medical management and prevent long-term complications. This study aimed to identify noninvasive markers that could predict postoperative disease activity. Methods Inclusion criteria were a diagnosis of CD, first ICR, interval colonoscopy, and whole transcriptome array meeting quality control standards. Demographic and clinical data were obtained from the electronic medical record. RNA extraction and human transcriptome microarray were performed on noninflamed ileal margins from operative specimens. Clinical data and random forest were analyzed in R. Principal components analysis, hierarchical clustering, and pathway enrichment were performed in Partek. Results Sixty-five patients completed the study, and 5 were excluded from analysis due to extreme variability on whole transcriptome analysis. Unsupervised hierarchical clustering revealed that patients with an i0 Rutgeerts score generally segregated from all others. In anti-TNF-naïve patients, unsupervised hierarchical clustering revealed complete segregation of patients with an i0 score. Reduced escalation in therapy and continued mucosal remission, consistent with indolent disease, were seen in the 4 years following surgery. Random forest identified 30 transcripts differentiating i0 patients from the other groups. Pathway enrichment highlighted toll-like receptor, NOD-like receptor, and TNF signaling. This transcriptome signature did not identify i0 anti-TNF-exposed patients. However, anti-TNF-exposed patients with indolent postoperative courses were found to have a transcriptome signature distinct from those with aggressive disease. Conclusions Anti-TNF-naïve and-exposed patients have unique expression profiles at the time of surgery, which may offer predictive value in assessing the risk of nonrecurrence.
KW - Crohn's disease
KW - recurrence
KW - surgery
UR - http://www.scopus.com/inward/record.url?scp=85058592555&partnerID=8YFLogxK
U2 - 10.1093/ibd/izy228
DO - 10.1093/ibd/izy228
M3 - Article
C2 - 29982468
AN - SCOPUS:85058592555
SN - 1078-0998
VL - 25
SP - 180
EP - 193
JO - Inflammatory bowel diseases
JF - Inflammatory bowel diseases
IS - 1
ER -