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Validated gene expression biomarker analysis in ulcerative colitis

The latest issue of the Alimentary Pharmacology & Therapeutics validated methods for measuring changes in gene expression in colonic biopsy samples.

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Accurate and reproducible measurement of expression of pro-inflammatory cytokines in colonic biopsies from patients with ulcerative colitis is essential for proof-of-concept and mechanism-of-action studies.

Few studies have rigorously established the number of biopsies required for accurate and reproducible biomarker measurements.

Dr Chang and colleagues from California, USA validated methods for measuring changes in gene expression in colonic biopsy samples.

The team obtained 12 colonic biopsies from each of 6 healthy controls, 6 patients with inactive UC, and 7 patients with active ulcerative colitis.

Mayo endoscopic scores were used as a clinical reference standard.

Inflammatory biomarkers correlate with Mayo endoscopic subscores for each colonic region
Alimentary Pharmacology & Therapeutics

Quantitative PCR was used to assess mRNA expression of 8 known inflammatory genes.

The researchers found that power to detect a reduction in gene expression in active vs inactive UC was calculated using a linear mixed effect model.

mRNA analysis of colonic biopsies is a sensitive and feasible approach for measuring inflammatory gene expression in colonic biopsies.

The team noted that inflammatory biomarkers correlate with Mayo endoscopic subscores for each colonic region.

For most genes, 3 rectal biopsies from 2 to 4 patients are required to detect changes in gene expression corresponding to active vs. inactive ulcerative colitis to achieve a power of 80% with an alpha of 0.05.

Dr Chang's team concludes, "Our data suggest that systematic measurement of inflammatory biomarkers at the mRNA level can be a valuable tool for hypothesis testing, and assessment of clinical activity and response to therapy in ulcerative colitis."

Aliment Pharmacol Ther 2014: 40(5): 477485
15 August 2014

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