title: Clinicopathologic significance of TRAP1 expression in colorectal cancer: a large scale study of human colorectal adenocarcinoma tissues.
abstract: BACKGROUND
  Colorectal cancer is the major cause of cancer mortality, despite development of therapeutic strategies. The novel marker tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein that has been related to drug resistance and protection from apoptosis in colorectal cancer. This study aims to delineate the clinicopathologic significance of TRAP1 expression in colorectal cancer.
  
  
  METHODS
  Seven-hundred and fourteen FFPE tissues were collected from colorectal cancer patients who underwent surgery from February 2002 to July 2011 at Dong-A University Medical Center, Busan, South Korea. We performed TRAP1 immunohistochemistry using tissue microarray, and divided into two groups, TRAP1 high expression group and low expression group. Statistical analysis was utilized to evaluate the association of TRAP1 with clinicopathologic characteristics and disease-specific survival of patients.
  
  
  RESULTS
  High TRAP1 expression was observed in 564 cases (79%) and low expression was 150 cases (21%). TRAP1 expression was significantly increased in colorectal cancer with advanced pathologic T-stage compared with that in early T-stage (p = 0.008). By univariate survival analysis, high TRAP1 expression was significantly associated with worse disease-specific survival (p = 0.01). But, TRAP1 expression was marginally associated with lymph node involvement and tumor differentiation (p = 0.085, p = 0.082, respectively). Multivariate analysis indicated that TRAP1 expression (hazard ratio, 1.947; 95% CI, 1.270 to 2.984; p = 0.002), and pathologic T stage (hazard ratio, 3.190; 95% CI, 1.275 to 7.983; p = 0.013) were independent prognostic factors for colorectal adenocarcinomas.
  
  
  CONCLUSIONS
  Here, we found that overexpression of TRAP1 might contribute to tumor cell local invasion of colorectal cancer. The association between TRAP1 overexpression and worse disease-specific survival also suggested that TRAP1 protein expression might have oncogenic role. Consequently, our data demonstrated that TRAP1 expression was a good prognostic biomarker for depth of invasion and disease-specific survival in colorectal cancer.
authors.affiliation: Department of Pathology, Dong-A University College of Medicine, 26 Daesingongwon-ro, Seo-gu, Busan, 49201, South Korea.
authors.forename: Min Gyoung
authors.initials: MG
authors.lastname: Pak
authors.affiliation: Department of Parmacology, Dong-A University College of Medicine, Busan, South Korea.
authors.forename: Hyong Jong
authors.initials: HJ
authors.lastname: Koh
authors.affiliation: Department of Pathology, Dong-A University College of Medicine, 26 Daesingongwon-ro, Seo-gu, Busan, 49201, South Korea. msroh@dau.ac.kr.
authors.forename: Mee Sook
authors.initials: MS
authors.lastname: Roh
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018841:HSP90 Heat-Shock Proteins; C092306:TRAP1 protein, human
keywords: Colorectal cancer; Disease-specific survival; Local invasion; TRAP1 (tumor necrosis factor receptor-associated protein 1)