Predictive biomarkers for inflammatory bowel disease-associated dysplasia

One of the most severe complications of UC is the development of colorectal
cancer (CRC). The incidence of CRC in patients with UC is higher compared to
the healthy population, and in subgroups of UC patients the incidence is up to
7 times higher. The etiology of CRC in UC patients (colitis-associated cancer,
CAC) is different from that of patients with sporadic CRC, yet the mechanisms
have not been fully elucidated.

Understanding the complex etiology of CAC is highly relevant and a large unmet
clinical need. Understanding the disease is necessary to prevent CAC, to detect
CAC at an early stage, and to understand which patients are most at risk. This
group should undergo more frequent colonoscopy surveillance to detect lesions
before they develop into cancer.

CAC arises from a complex interplay between genetic, environmental (microbiome)
and immune-driven triggers/defects, and is even more complicated by the use of
different anti-inflammatory drugs. One of the problems of investigating CAC and
forcing breakthroughs in this field that lacks innovation, is that emerging
novel concepts (in for example the microbiome or immune-driven triggers for
CAC) are difficult to test because of the lack of patient*s materials from a
population in which prospective sampling is typically extremely time-consuming.

To collect biomaterials (peripheral blood, DNA, serum, faeces and intestinal
biopsies from IBD patients with dysplastic lesions in the colon to allow
research into the immunological pathways leading to dysplasia development.

This is a study based on a systems biology approach. Individual IBD patients
with undergoing consecutive routine care surveillance endoscopies will be
studied. Patients will only undergo colonoscopies if that is part of their
routine care.
In parallel to the collection of patients* phenotypic data and detailed
information on response to various treatments, mucosal biopsies from normal
and/or potentially dysplastic tissues or cancer will be collected and analysed
for cytokines and chemokines, cell types and mucosa associated microbiome.
Moreover, blood, serum and faeces will be stored for analysis of the genotype
(including whole genome methylome and transcriptome) the serum
cytokine/chemokine profile and the *luminal* faecal microbiome/metabolome.

Peripheral blood is sampled with a negligible risk and low burden.

Endoscopic biopsies taken during colonoscopy include a minimal risk of
complications, mainly bleeding or perforation (< 1: 10,000). In case
complication occurs, endoscopic treatment (hemostasis/clipping) is effective in
most cases. Rarely, hospital admission with/without surgical intervention,
antibiotic therapy and/or blood transfusion can be required.