Potential utility of DNA methytlation as a biomarker for prediction of ulcerative colitis associated colorectal carcinoma (UCAC)

Background/Aim: UC have increased risk of colorectal cancers. DNA methylation is deeply involved in carcinogenesis. To evaluate utility of DNA methylation as the risk marker for UCAC, we quantified DNA methylation of inflamed rectal mucosa, neoplastic tissue and adjacent colonic mucosa of UC. Method: Inflamed rectal mucosa (n=84) and normal proximal mucosa (n=10) of 84 cancer-free UC were examined. Neoplastic tissue (n=33) and adjacent mucosa (n=26) from 16 UC with neoplasia (UCAC or DALM) were also studied. Bisulfite pyro sequencing was performed for the quantification of 45 cancer or age-related candidate panels. Illumina Infinium Human Methylation 450 was used to determine 470,000 CpG sites. Results: Inflamed mucosa of UC was characterized as hyper methylation in candidate panels. Hyper methylation of many panels correlated with longer duration of disease and some panels showed hyper methyhlation in both neoplastic and adjacent tissue compared to rectal mucosa of cancer-free cases (DPYS, N33, both p<0.0001). Genome scale analysis revealed UC with severe inflammation or neoplasia presented hyper methylation at CpG sites rather than outside CpG. Gene ontology analysis demonstrated methylated promoters in UC encoded protein related to biosynthetic process (p=5.69E-05). Conclusion: Our data suggested the potential utility of DNA methytlation as a biomarker for prediction of UCAC. Enrichment of specific pathway in methylated genes raised the possibility of targeting therapy for UCAC.