August 10, 2018
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Biomarker panel may help diagnose colorectal cancer in high-risk IBD patients

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A panel of methylation biomarkers helped identify colorectal dysplasia and cancer in high risk patients with inflammatory bowel disease, according to research published in Inflammatory Bowel Diseases.

Gabriel Capellá, MD, PhD, of L’Hospitalet de Llobregat in Barcelona, Spain, and colleagues wrote that the panel could help physicians make an early diagnosis in this population where identifying polyps can be difficult.

“Patients with IBD can present dysplasia with different forms: localized, flat, diffuse, multifocal, or polypoid, making detection difficult for the pathologist and invisible for the endoscopist,” they wrote. “Some patients with [ulcerative colitis] or colonic [Crohn’s disease] may undergo more treatment/surveillance than needed, whereas others may not be monitored closely enough. Thus, biomarkers that can predict risk of CRC and improve surveillance planning for these patients are needed.”

In the discovery phase of the study, investigators examined 73 biopsies from 48 patients with IBD using genome-wide DNA methylation analysis to identify potential early risk markers for dysplasia or cancer. They identified five candidate methylation biomarkers: EYA4, SLIT2, FLI1, USP44 and SND1.

In the validation phase, Capellá and colleagues analyzed biopsies of 203 patients: 38 with IBD and associated neoplasia; 81 patients with IBD (25 with high risk); 48 with sporadic CRC; and 36 healthy controls.

Investigators found that prevalence of methylation was higher in patients with IBD and associated neoplasia both in diseased and adjacent health tissue (71% and 52%, respectively) compared with tissue taken from health controls (6%).

They also detected methylation more frequently in patients with IBD who were at high risk for dysplasia or cancer than in patients who were at lower risk (92% vs. 57%; OR = 8.63; P = .001). The difference in methylation levels was more evident in the healthy mucosa in high-risk patients compared with low-risk patients (82% vs. 15%), which highlights the need to test nonpathological mucosa in routine surveillance biopsies, the researchers wrote.

Capellá and colleagues wrote that this biomarker panel could compliment endoscopic surveillance and help individualize management of patients with different risk levels.

“Our study may help in the early identification of colorectal dysplasia or cancer in IBD patients at high risk of cancer or dysplasia by analyzing a new panel of methylated markers,” they wrote. “This promising panel of biomarkers should now be tested in a larger cohort of patients receiving standard of care biological treatments that presumably have a higher chemopreventive impact.” – by Alex Young

Disclosures: The authors report no relevant financial disclosures.