Abstract #1213: Mapping neoplastic progression of ulcerative colitis by quantitative proteomics

Abstract

Patients with ulcerative colitis (UC) have an increased risk for developing colorectal cancer. The cancer risk is sufficiently elevated to require UC patients to have life-long colonoscopic surveillance every 1-2 years. Because UC tumorigenesis is associated with molecular field defects that can extend throughout the entire colon, including the non-dysplastic mucosa; we hypothesized that the same field defect will include abnormally expressed proteins. We applied proteomics to study the protein expression of UC neoplastic progression. The protein profiles of colonic epithelium were compared from 1) UC patients without dysplasia (non-progressors); 2) histologically normal-appearing colonic tissue of UC patient with high-grade dysplasia or cancer (progressors); 3) high-grade dysplastic tissue from UC progressors and 4) normal colon. We identified gradual protein dysregulation associated with UC neoplastic progression. Proteins relating to mitochondrion, oxidative activity, DNA repair, calcium ion binding were some of interesting classes of these dysregulated proteins. Network analysis discovered that Sp1 and c-myc proteins may play important roles in UC early and late stages of neoplastic progression, respectively. Finally, two up-regulated proteins in the non-dysplastic tissue of UC progressors, CPS1 and S100P, were further validated by IHC analysis. S100P could achieve 100% specificity and 80% sensitivity in distinguishing the non-dysplastic biopsies from progressors compared to non-progressors and normal colon. Our study provides insight into the molecular events associated with UC neoplastic progression, which could be exploited for the development of protein biomarkers in fields of non-dysplastic mucosa that identify a patient\#8217;s risk for UC dysplasia.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1213.