title: An ileal Crohn's disease gene signature based on whole human genome expression profiles of disease unaffected ileal mucosal biopsies.
abstract: Previous genome-wide expression studies have highlighted distinct gene expression patterns in inflammatory bowel disease (IBD) compared to control samples, but the interpretation of these studies has been limited by sample heterogeneity with respect to disease phenotype, disease activity, and anatomic sites. To further improve molecular classification of inflammatory bowel disease phenotypes we focused on a single anatomic site, the disease unaffected proximal ileal margin of resected ileum, and three phenotypes that were unlikely to overlap: ileal Crohn's disease (ileal CD), ulcerative colitis (UC), and control patients without IBD. Whole human genome (Agilent) expression profiling was conducted on two independent sets of disease-unaffected ileal samples collected from the proximal margin of resected ileum. Set 1 (47 ileal CD, 27 UC, and 25 Control non-IBD patients) was used as the training set and Set 2 was subsequently collected as an independent test set (10 ileal CD, 10 UC, and 10 control non-IBD patients). We compared the 17 gene signatures selected by four different feature-selection methods to distinguish ileal CD phenotype with non-CD phenotype. The four methods yielded different but overlapping solutions that were highly discriminating. All four of these methods selected FOLH1 as a common feature. This gene is an established biomarker for prostate cancer, but has not previously been associated with Crohn's disease. Immunohistochemical staining confirmed increased expression of FOLH1 in the ileal epithelium. These results provide evidence for convergent molecular abnormalities in the macroscopically disease unaffected proximal margin of resected ileum from ileal CD subjects.
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhang
authors.forename: Bowen
authors.initials: B
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.forename: Qing Qing
authors.initials: QQ
authors.lastname: Gong
authors.forename: Christopher
authors.initials: C
authors.lastname: Morando
authors.forename: Themistocles
authors.initials: T
authors.lastname: Dassopoulos
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Newberry
authors.forename: Steven R
authors.initials: SR
authors.lastname: Hunt
authors.forename: Ellen
authors.initials: E
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D015894:Genome, Human; D055106:Genome-Wide Association Study; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D043425:Glutamate Carboxypeptidase II