title: Correlation between mitochondrial TRAP-1 expression and lymph node metastasis in colorectal cancer.
abstract: OBJECTIVE
  To evaluate the effect of mitochondrial tumor necrosis factor receptor-associated protein-1 (TRAP-1) on the lymph node metastasis (LNM) in Chinese colorectal cancer (CRC) patients, and develop potential LNM-associated biomarkers for CRC using quantitative real-time polymerase chain reaction (RT-PCR) analysis.
  
  
  METHODS
  Differences in mitochondrial TRAP-1 gene expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed in 96 Chinese colorectal carcinoma samples using quantitative RT-PCR analysis, Western blotting, and confirmed with immunohistochemical assay. The relationship between clinicopathological parameters and potential diagnostic biomarkers was also examined.
  
  
  RESULTS
  TRAP-1 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by RT-PCR, Western blotting and immunohistochemical assay. The expression of TRAP-1 in two different metastatic potential human colorectal cancer cell lines, LoVo and HT29, was analyzed with Western blotting. The expression level of TRAP-1 was dramatically higher in LoVo than in HT29. Overexpression of TRAP-1 was significantly associated with LNM (90.2% in LNM group vs 22% in non-LNM group, P < 0.001), the advanced tumor node metastasis stage (89.1% in LNM group vs 26.9% in non-LNM group, P < 0.001), the increased 5-year recurrence rate (82.7% in LNM group vs 22.6% in non-LNM group, P < 0.001) and the decreased 5-year overall survival rate (48.4% in LNM vs 83.2% in non-LNM group, P < 0.001). Univariate and multivariate analyses indicated that TRAP-1 expression was an independent prognostic factor for recurrence and survival of CRC patients (Hazard ratio of 2.445 in recurrence, P = 0.017; 2.867 in survival, P = 0.028).
  
  
  CONCLUSIONS
  Mitochondria TRAP-1 affects the lymph node metastasis in CRC, and may be a potential biomarker for LNM and a prognostic factor in CRC. Over-expression of TRAP-1 is a predictive factor for the poor outcome of colorectal cancer patients.
authors.affiliation: Department of Colorectal Cancer, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Gao
authors.forename: Bao-Rong
authors.initials: BR
authors.lastname: Song
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Peng
authors.forename: Yuan-Ming
authors.initials: YM
authors.lastname: Lu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D016009:Chi-Square Distribution; D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary* / Q000601:surgery; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger; C092306:TRAP1 protein, human
keywords: Colorectal cancer; Hsp90 family; Lymph node metastasis; Mitochondria tumor necrosis factor receptor-associated protein-1; Prognosis; Quantitative real-time polymerase chain reaction analysis