Epigenetic regulation of WNT signaling pathway genes in inflammatory bowel disease (IBD) associated neoplasia.

Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract
Mashaal DhirNita Ahuja

Abstract

WNT signaling pathway dysregulation is an important event in the pathogenesis of colorectal cancer (CRC) with APC mutations seen in more than 80% of sporadic CRC. However, such mutations in the WNT signaling pathway genes are rare in inflammatory bowel disease (IBD) associated neoplasia (dysplasia and cancer). This study examined the role of epigenetic silencing of WNT signaling pathway genes in the pathogenesis of IBD-associated neoplasia. Paraffin-embedded tissue samples were obtained and methylation of ten WNT signaling pathway genes, including APC1A, APC2, SFRP1, SFRP2, SFRP4, SFRP5, DKK1, DKK3, WIF1 and LKB1, was analyzed. Methylation analysis was performed on 41 IBD samples, 27 normal colon samples (NCs), and 24 sporadic CRC samples. Methylation of WNT signaling pathway genes is a frequent and early event in IBD and IBD-associated neoplasia. A progressive increase in the percentage of methylated genes in the WNT signaling pathway from NCs (4.2%) to IBD colitis (39.7%) to IBD-associated neoplasia (63.4%) was seen (NCs vs. IBD colitis, p < 0.01; IBD colitis vs. IBD-associated neoplasia, p = 0.01). In the univariate logistic regression model, methylation of APC2 (OR 4.7, 95% CI: 1.1-20.63, p = 0.04), SFRP1 (OR 5.1, 95% CI: 1...Continue Reading

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