Proteins that underlie neoplastic progression of ulcerative colitis

Teresa A. Brentnall, Sheng Pan, Mary P. Bronner, David A. Crispin, Hamid Mirzaei, Kelly Cooke, Yasuko Tamura, Tatiana Nikolskaya, Lellean JeBailey, David R. Goodlett, Martin McIntosh, Ruedi Aebersold, Peter S. Rabinovitch, Ru Chen

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Patients with ulcerative colitis (UC) have an increased risk for developing colorectal cancer. Because UC tumorigenesis is associated with genomic field defects that can extend throughout the entire colon, including the non-dysplastic mucosa, we hypothesized that the same field defects will include abnormally expressed proteins. Here, we applied proteomics to study the protein expression of UC neoplastic progression. The protein profiles of colonic epithelium were compared with (i) UC patients without dysplasia (non-progressors), (ii) nondysplastic colonic tissue from UC patient with high-grade dysplasia or cancer (progressors), (iii) high-grade dysplastic tissue from UC progressors, and (iv) normal colon. We identified differential protein expression associated with UC neoplastic progression. Proteins relating to mitochondria, oxidative activity, and calcium-binding proteins were some of the interesting classes of these proteins. Network analysis discovered that Sp1 and c-myc proteins may play roles in UC early and late stages of neoplastic progression, respectively. Two over-expressed proteins in the non-dysplastic tissue of UC progressors, carbamoyl-phosphate synthase 1 and S100P, were further confirmed by immunohistochemistry analysis. 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's risk for UC dysplasia.

Original languageEnglish (US)
Pages (from-to)1326-1337
Number of pages12
JournalProteomics - Clinical Applications
Volume3
Issue number11
DOIs
StatePublished - Dec 2009

Keywords

  • Biomarker
  • Cancer
  • Dysplasia
  • Neoplastic progression
  • Ulcerative colitis

ASJC Scopus subject areas

  • Clinical Biochemistry

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