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Molecular Comparison of Ulcerative Colitis Different in Age and Extent of Disease by Colon Biopsy mRNA Expression Profiling Richard Strauss, MD Disclosure: Janssen Research and Development Adult vs. Pediatric UC Data Compatibility Adult


  1. Molecular Comparison of Ulcerative Colitis Different in Age and Extent of Disease by Colon Biopsy mRNA Expression Profiling Richard Strauss, MD Disclosure: Janssen Research and Development

  2. Adult vs. Pediatric UC – Data Compatibility Adult UC Pediatric UC Data Sim poni UC T1 7 GSE1 0 6 1 6 * Data type Colon biopsy Colon biopsy Platform (all in situ Affymetrix HT HG Affymetrix HG U133 oligonucleotide) U133+ PM array Plus 2 Total # of probes 54,715 54,675 Analysis In-house In-house Analysis cutoff | FC| > 2x, adjust | FC| > 2x, adjust p< 0.05 p< 0.05 Sample size 87 UC, 21 normal 10 UC, 11 normal Disease profile 2253 probe sets 2129 probe sets *Data extracted from Nature Genetics 2008

  3. Top Ranked Canonical Pathways in Adult and Pediatric UC P-values based on Fisher’s exact test 0.0 25.5 -log(p-value)< 1.3 considered significant enrichment (p-value < 0.05)

  4. Common Upstream Expression Molecules Observed in Adult and Pediatric UC -7.64 0 12.84 Activation z-score inhibited activated

  5. Extensive vs. Local Disease: Adult Patients Dataset: C0154T17 ADULT ULCERATIVE COLITIS STUDY, BASELINE SAMPLES Avg Limited 14 Correlation=0.9915 12 PValue=0.0000e+000 10 Avg Limited 8 6 4 2 0 ExtentDisease 0 2 4 6 8 10 12 14 Avg Extensive • Disease profile in extensive UC is high correlated with that in local disease • Unsupervised clustering of the disease profile shows no segregation of extensive (n= 27) vs. limited (n= 60) UC in adult patients.

  6. Extensive vs. Local Disease: Pediatric Subjects Dataset: CNTO148UC01001 PEDIATRIC ULCERATIVE COLITIS STUDY, BASELINE SAMPLES avg.EXTENSIVE 14 Correlation=0.9750 12 PValue=0.0000e+000 10 avg.LIMITED UC 8 6 4 2 Disease Extension 0 2 4 0 6 8 10 12 14 • Disease profile in extensive UC is high correlated with that in local disease • Unsupervised clustering of the disease profile shows no segregation of extensive (n= 13) vs. limited (n= 7) UC in adult patients.

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  8. Figure 2A Top Canonical Pathw ays in Pediatric and Adult UC B Cell Development^ Leukocyte Hepatic Fibrosis / 30 Extravasation Hepatic Stellate Cell Signaling^ Activation* ^ 25 Granulocyte Adhesion 20 TREM1 Signaling^ and Diapedesis* ^ 15 Role of Macrophages, 10 Agranulocyte Fibroblasts and Adhesion and Endothelial Cells in 5 Diapedesis* ^ RA^ 0 Diff. Reg. of Cytokine Production in Atherosclerosis Intestinal Epithelial Signaling* ^ Cells by IL-17A/ F* Altered T Cell and B Inhibition of Matrix Cell Signaling in Metalloproteases* RA* ^ LPS/ I L-1 Mediated Dendritic Cell Inhibition of RXR Maturation* ^ Function* Pediatric UC (GSE10616) Role of IL-17A in Adult UC (C0524T17) Psoriasis* Significant Enrichment Cutoff

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