Abstract
BackgroundThere are no biomarkers to facilitate the identification of patients with ulcerative colitis (UC) who are at high risk for developing colorectal cancer (CRC). In our current study, we used rectal tissues from UC patients to identify aberrant DNA methylations and evaluated whether they could be used to identify UC patients with coexisting colorectal neoplasia.ResultsUsing a training set, we identified 484 differentially methylated regions (DMRs) with absolute delta beta-values > 0.1 in rectal mucosa by using the ChAMP algorithm. Next, pathway enrichment analysis was performed using 484 DMRs to select coordinately methylated DMRs, resulting in the selection of 187 aberrant DMRs in rectal tissues from UC-CRC. Then, the Elastic Net classification algorithm was performed to narrow down optimal aberrant DMRs, and we finally selected 11 DMRs as biomarkers for identification of UC-CRC patients. The 11 chosen DMRs could discriminate UC patients with or without CRC in a training set (area under the curve, 0.96) and the validation set (area under the curve, 0.81).ConclusionsIn conclusion, we identified 11 DMRs that could identify UC patients with CRC complications. Prospective studies should further confirm the validity of these biomarkers.MethodsWe performed genome-wide DNA methylation profiles in rectal mucosal tissues (n = 48) from 24 UC-CRC and 24 UC patients in a training set. Next, we performed comprehensive DNA methylation analysis using rectal mucosal tissues (n = 16) from 8 UC-CRC and 8 UC patients for validation.
Highlights
Patients with long-standing ulcerative colitis (UC) are at a higher risk than the general population for developing colorectal cancer (CRC)
The Elastic Net classification algorithm was performed to narrow down optimal aberrant differentially methylated regions (DMRs), and we selected 11 DMRs as biomarkers for identification of UC-CRC patients
We examined the possibility of using genome-wide DNA methylation array analysis of rectal tissues of UC patients to identify aberrant DNA methylation and thereby identify UC patients who had coexisting colorectal neoplasia
Summary
Patients with long-standing ulcerative colitis (UC) are at a higher risk than the general population for developing colorectal cancer (CRC). The prevalence of colitis-associated cancer (CAC) in patients with UC is 8% 20 years after the initial UC diagnosis and increases to 18% at 30 years [1]. Surveillance colonoscopy with multiple random biopsies has been widely recommended for patients with long-standing and extensive UC [4]. The low yield and lack of clinical consequences from random biopsies in this high-risk population raise questions about the necessity and cost-effectiveness of such UC surveillance [5]. There are no biomarkers to facilitate the identification of patients with ulcerative colitis (UC) who are at high risk for developing colorectal cancer (CRC). We used rectal tissues from UC patients to identify aberrant DNA methylations and evaluated whether they could be used to identify UC patients with coexisting colorectal neoplasia
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