title: Up-regulation of mitochondrial chaperone TRAP1 in ulcerative colitis associated colorectal cancer.
abstract: OBJECTIVE
  To characterize tumor necrosis factor receptor-associated protein 1 (TRAP1) expression in the progression of ulcerative colitis (UC)-associated colorectal cancer.
  
  
  METHODS
  Chronic UC is an inflammatory bowel disease that predisposes to colorectal cancer. Immunohistochemical analysis was used to evaluate TRAP1 expression on tissue microarrays containing colonic tissues from 42 UC progressors (patients with cancer or dysplasia) and 38 non-progressors (dysplasia/cancer free patients). Statistical analyses of the TRAP1 immunohistochemistry staining were performed using GraphPad Prism. Differences in the TRAP1 level between non-progressors and progressors were tested for statistical significance using the Mann-Whitney test. Receiver operating characteristic curve method was used to quantify marker performance in distinguishing diseased cases from controls.
  
  
  RESULTS
  TRAP1 was up-regulated in the colon tissues from UC progressors, but not in the colon tissues from UC non-progressors. Moreover, up-regulation of TRAP1 preceded the neoplastic changes: it was present in both the dysplastic and non-dysplastic tissues of UC progressors. When TRAP1 staining in rectal tissue was used as a diagnostic marker, it could distinguish progressors from non-progressors with 59% sensitivity and 80% specificity. Our study further showed that the increase of TRAP1 expression positively correlated with the degree of inflammation in the colorectal cancer tissues, which could be related to the increased oxidation present in the colonic mucosa from UC progressors. We then investigated the cellular proteome changes underlying oxidative stress, and found that oxidative stress could induce up-regulation of TRAP1 along with several other negative modulators of apoptosis.
  
  
  CONCLUSIONS
  These results suggest that oxidative stress in long standing UC could lead to the increase of cytoprotective protein TRAP1, which in turn could promote cancer progression by preventing or protecting the oxidative damaged epithelial cells from undergoing apoptosis. TRAP1 could be a potential diagnostic marker for UC associated colorectal cancer.
authors.affiliation: Ru Chen, Sheng Pan, Lisa A Lai, David A Crispin, Teresa A Brentnall, Department of Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: Ru
authors.initials: R
authors.lastname: Chen
authors.affiliation: Ru Chen, Sheng Pan, Lisa A Lai, David A Crispin, Teresa A Brentnall, Department of Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: Sheng
authors.initials: S
authors.lastname: Pan
authors.affiliation: Ru Chen, Sheng Pan, Lisa A Lai, David A Crispin, Teresa A Brentnall, Department of Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: Keith
authors.initials: K
authors.lastname: Lai
authors.affiliation: Ru Chen, Sheng Pan, Lisa A Lai, David A Crispin, Teresa A Brentnall, Department of Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lai
authors.affiliation: Ru Chen, Sheng Pan, Lisa A Lai, David A Crispin, Teresa A Brentnall, Department of Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Crispin
authors.affiliation: Ru Chen, Sheng Pan, Lisa A Lai, David A Crispin, Teresa A Brentnall, Department of Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: Mary P
authors.initials: MP
authors.lastname: Bronner
authors.affiliation: Ru Chen, Sheng Pan, Lisa A Lai, David A Crispin, Teresa A Brentnall, Department of Medicine, University of Washington, Seattle, WA 98195, United States.
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Brentnall
mesh_terms: D017209:Apoptosis; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D003093:Colitis, Ulcerative / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D018450:Disease Progression; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D012007:Rectum / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D018841:HSP90 Heat-Shock Proteins; C092306:TRAP1 protein, human
keywords: Colorectal cancer; Inflammation; Oxidative stress; Tumor necrosis factor receptor-associated protein 1; Ulcerative colitis