Abstract
BackgroundColorectal 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.MethodsSeven-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.ResultsHigh 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.ConclusionsHere, 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.
Highlights
Colorectal cancer is the major cause of cancer mortality, despite development of therapeutic strategies
We evaluated the correlation between tumor necrosis factor receptor-associated protein 1 (TRAP1) expression and various clinicopathologic factors to assess the diagnostic and prognostic significance of TRAP1
Cox proportional hazard regression analysis indicated that TRAP1 expression, and pathologic T stage were independent prognostic factors for colorectal adenocarcinomas (Table 2)
Summary
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. Colorectal cancer is one of the most commonly diagnosed cancers along with breast, lung and bronchus cancers in men and women. In 2016, colorectal cancer is still a major cause of cancer death in men and women [1]. Tumor necrosis factor receptor associated protein 1 (TRAP1) is a molecular chaperone of the 90 kDa heat shock protein (HSP90) family, and is mostly localized to the mitochondrial matrix. Further sequence analysis revealed that TRAP1 was identical to heat shock protein 75 (HSP75) [3]. TRAP1 modulates the permeability transition pore of mitochondrial inner membrane, and protects the mitochondrial structure from excessive reactive oxygen species (ROS) induced cell death, such as in Parkinson’s disease and cancers [4, 5]
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