TY - JOUR
T1 - Proteins that underlie neoplastic progression of ulcerative colitis
AU - Brentnall, Teresa A.
AU - Pan, Sheng
AU - Bronner, Mary P.
AU - Crispin, David A.
AU - Mirzaei, Hamid
AU - Cooke, Kelly
AU - Tamura, Yasuko
AU - Nikolskaya, Tatiana
AU - JeBailey, Lellean
AU - Goodlett, David R.
AU - McIntosh, Martin
AU - Aebersold, Ruedi
AU - Rabinovitch, Peter S.
AU - Chen, Ru
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
KW - Biomarker
KW - Cancer
KW - Dysplasia
KW - Neoplastic progression
KW - Ulcerative colitis
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U2 - 10.1002/prca.200900061
DO - 10.1002/prca.200900061
M3 - Article
C2 - 20098637
AN - SCOPUS:77951049868
SN - 1862-8346
VL - 3
SP - 1326
EP - 1337
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
IS - 11
ER -