Colorectal Cancer
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 28, 2007; 13(20): 2803-2810
Published online May 28, 2007. doi: 10.3748/wjg.v13.i20.2803
Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity
Michiko Aizawa, Masami Hoshino, Shinji Ohki, Seiichi Takenoshita, Max Costa, Yasufumi Utsumi, Keiichirou Morimura, Kensuke Kumamoto, Minori Koshiji, Kam-Meng Tchou-Wong, Curtis C Harris, David Piquemal, Thérèse Commes
Minori Koshiji, Kam-Meng Tchou-Wong, Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, United States
Kensuke Kumamoto, Shinji Ohki, Seiichi Takenoshita, Second Department of Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1295, Japan
Kensuke Kumamoto, Curtis C Harris, National Institutes of Health, National Cancer Institute, Building 37, Bethesda, MD 20892, United States
Keiichirou Morimura, Department of Pathology, Osaka City University, Osaka, Japan
Yasufumi Utsumi, Michiko Aizawa, Department of Pathology, Ohara General Hospital, 6-11 Ohmachi, Fukushima 960-8611, Japan
Masami Hoshino, Department of Surgery, Ohara General Hospital, 6-11 Ohmachi, Fukushima 960-8611, Japan
Thérèse Commes, David Piquemal, University Montpellier II, Montpellier, France
Author contributions: All authors contributed equally to the work.
Supported by grant numbers ES00260 (Costa and Tchou-Wong), ES05512 (Costa), ES10344 (Costa), and T32-ES07324 (Costa and Tchou-Wong) from the National Institutes of Environmental Health Sciences and CA16087 (Costa) from the National Cancer Institute, as well as DK63603 (Tchou-Wong) and CA101234 (Tchou-Wong) from the National Institutes of Health
Correspondence to: Dr. Kam-Meng Tchou-Wong, Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, United States. tchouk02@med.nyu.edu
Telephone: +1-845-7313504 Fax: +1-845-3512218
Received: February 2, 2007
Revised: February 25, 2007
Accepted: March 1, 2007
Published online: May 28, 2007
Abstract

AIM: To evaluate the role of N-myc downstream-regulated gene 1 (NDRG1) expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds.

METHODS: Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1α (HIF-1α), we examined NDRG1 expression together with p53 and HIF-1α by immunohistochemistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed.

RESULTS: NDRG1 protein was significantly increased in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion, venous invasion, depth of invasion, histopathological type, and Dukes' stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type, Dukes' stage and HIF-1α expression in US-Caucasian patients but not in US-African American patients. Interestingly, Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups. However, in p53-positive US cases, NDRG1 positivity correlated significantly with better survival. In addition, NDRG1 expression also correlated significantly with improved survival in US patients with stages III and IV tumors without chemotherapy. In Japanese patients with stages II and III tumors, strong NDRG1 staining in p53-positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy.

CONCLUSION: NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer patients with different ethnic backgrounds.

Keywords: NDRG1 expression; Colorectal cancer; Race; Ethnicity; Clinical outcomes