Molecular Comparison of Ulcerative Colitis Different in Age and - - PowerPoint PPT Presentation

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Molecular Comparison of Ulcerative Colitis Different in Age and - - PowerPoint PPT Presentation

Nov 16, 2023 103 likes •202 views

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

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Molecular Comparison of Ulcerative Colitis Different in Age and Extent of Disease by Colon Biopsy mRNA Expression Profiling

Disclosure: Janssen Research and Development Richard Strauss, MD

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Adult vs. Pediatric UC – Data Compatibility

Data

Adult UC Pediatric UC

Sim poni UC T1 7 GSE1 0 6 1 6 * Data type Colon biopsy Colon biopsy Platform (all in situ

  • ligonucleotide)

Affymetrix HT HG U133+ PM array Affymetrix HG U133 Plus 2 Total # of probes 54,715 54,675 Analysis In-house In-house Analysis cutoff | FC| > 2x, adjust p< 0.05 | FC| > 2x, adjust 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

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Top Ranked Canonical Pathways in Adult and Pediatric UC

P-values based on Fisher’s exact test

  • log(p-value)< 1.3 considered significant enrichment (p-value < 0.05)

0.0 25.5

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Common Upstream Expression Molecules Observed in Adult and Pediatric UC

  • 7.64

12.84

Activation z-score inhibited activated

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Extensive vs. Local Disease: Adult Patients

  • 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.

ExtentDisease

Avg Limited

2 4 6 8 10 12 14

Avg Extensive

2 4 6 8 10 12 14

Avg Limited

Correlation=0.9915 PValue=0.0000e+000

Dataset: C0154T17 ADULT ULCERATIVE COLITIS STUDY, BASELINE SAMPLES

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SLIDE 6

Extensive vs. Local Disease: Pediatric Subjects

  • 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.

2 4 6 8 10 12 14 2 4 6 8 10 12 14 avg.LIMITED UC avg.EXTENSIVE

Correlation=0.9750 PValue=0.0000e+000

Disease Extension

Dataset: CNTO148UC01001 PEDIATRIC ULCERATIVE COLITIS STUDY, BASELINE SAMPLES

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Backup

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5 10 15 20 25 30 B Cell Development^ Leukocyte Extravasation Signaling^ TREM1 Signaling^ Role of Macrophages, Fibroblasts and Endothelial Cells in RA^

  • Diff. Reg. of Cytokine

Production in Intestinal Epithelial Cells by IL-17A/ F* Altered T Cell and B Cell Signaling in RA* ^ Dendritic Cell Maturation* ^ Role of IL-17A in Psoriasis* LPS/ I L-1 Mediated Inhibition of RXR Function* Inhibition of Matrix Metalloproteases* Atherosclerosis Signaling* ^ Agranulocyte Adhesion and Diapedesis* ^ Granulocyte Adhesion and Diapedesis* ^ Hepatic Fibrosis / Hepatic Stellate Cell Activation* ^

Top Canonical Pathw ays in Pediatric and Adult UC

Pediatric UC (GSE10616) Adult UC (C0524T17) Significant Enrichment Cutoff

Figure 2A