Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 7, 2012; 18(41): 5965-5971
Published online Nov 7, 2012. doi: 10.3748/wjg.v18.i41.5965
Correlation between mitochondrial TRAP-1 expression and lymph node metastasis in colorectal cancer
Jing-Yan Gao, Bao-Rong Song, Jun-Jie Peng, Yuan-Ming Lu
Jing-Yan Gao, Bao-Rong Song, Jun-Jie Peng, Yuan-Ming Lu, Department of Colorectal Cancer, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China
Jing-Yan Gao, Department of Human Anatomy and Histo-Embryology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Bao-Rong Song, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Author contributions: Lu YM designed research, analyzed data and wrote the paper; Gao JY and Song BR did the experiments; Peng JJ collected the sample.
Supported by The Grants from Shanghai Health Bureau, No. JG1103
Correspondence to: Yuan-Ming Lu, PhD, Department of Colorectal Cancer Center, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Dong’an Road 270, Shanghai 200032, China. bobojpn@hotmail.com
Telephone: +86-21-64175590 Fax: +86-21-64035387
Received: November 7, 2011
Revised: March 23, 2012
Accepted: May 12, 2012
Published online: November 7, 2012
Abstract

AIM: 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).

CONCLUSION: 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.

Keywords: Colorectal cancer; Lymph node metastasis; Prognosis; Quantitative real-time polymerase chain reaction analysis; Hsp90 family; Mitochondria tumor necrosis factor receptor-associated protein-1