Togo N, Ohwada S, Sakurai S, Toya H, Sakamoto I, Yamada T, Nakano T, Muroya K, Takeyoshi I, Nakajima T, Sekiya T, Yamazumi Y, Nakamura T, Akiyama T. Prognostic significance of BMP and activin membrane-bound inhibitor in colorectal cancer. World J Gastroenterol 2008; 14(31): 4880-4888 [PMID: 18756595 DOI: 10.3748/wjg.14.4880]
Corresponding Author of This Article
Susumu Ohwada, Department of Surgery, Graduate School of Medicine, Gunma University, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan. go.go.ohwada@gmail.com
Article-Type of This Article
Colorectal Cancer
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Nozomi Togo, Susumu Ohwada, Hiroyuki Toya, Ichiro Sakamoto, Tatsuya Yamada, Tetsuhiro Nakano, Ken Muroya, Izumi Takeyoshi, Departments of Surgery, Graduate School of Medicine, Gunma University, Gunma 371-8511, Japan
Shinji Sakurai, Takashi Nakajima, Departments of Tumor Pathology, Graduate School of Medicine, Gunma University, Gunma 371-8511, Japan
Takashi Sekiya, Yusuke Yamazumi, Tsutomu Nakamura, Tetsu Akiyama, Laboratory of Molecular and Genetic Information, Institute for Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan
Author contributions: Togo N and Ohwada S contributed equally to this work; Togo N, Ohwada S, Sakurai S, Toya H, Nakajima T and Akiyama T designed research; Togo N, Toya H, Muroya K performed research; Akiyama T contributed new reagents; Togo N, Ohwada S, Nakajima T and Akiyama T analyzed data and wrote the paper.
Supported by Grants from the Japan Science and Technology Agency, No. 17014011; The Harunasou Foundation Cancer Research Subsidizing Fund; The Kanetsu Chuo Hospital Research Fund; And research funds from the Uchida Clinic in Inamachi, Saitama; The Katoh Clinic, Maebashi Norte Hospital in Maebashi, Gunma; And Keiaido Hospital in Midori, Gunma
Correspondence to: Susumu Ohwada, Department of Surgery, Graduate School of Medicine, Gunma University, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan. go.go.ohwada@gmail.com
Telephone: +81-279-233030 Fax: +81-279-232740
Received: May 23, 2008 Revised: August 12, 2008 Accepted: August 17, 2008 Published online: August 21, 2008
Abstract
AIM: To investigate the clinical significance of BMP and activin membrane-bound inhibitor (BAMBI) which is a pseudoreceptor of transforming growth factor-beta (TGF-β) type I receptors and acts as a negative regulator of TGF-β signaling and expression aberrantly elevated in colorectal cancers (CRCs). We studied BAMBI expression in CRCs.
METHODS: We studied BAMBI expression in 183 surgically resected CRCs by immunochemical and immunoblotting analyses using a generated monoclonal anti-BAMBI antibody. Commercially available anti-β-catenin and anti-p53 antibodies were also applied for immunochemical analyses as a comparison control.
RESULTS: Immunohistochemical analysis revealed that BAMBI expression was observed in 148 (80.8%), and strong BAMBI expression was observed in 46% of the CRCs. Strong BAMBI expression was positively correlated with histological type, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (P < 0.05). Clear associations were found between BAMBI and β-catenin (P = 0.035) and p53 (P = 0.049) expression. In curatively resected CRC, 5-year recurrence-free survival was 51.9% (P = 0.037) for strong BAMBI expression compared to 79.8% for weak BAMBI expression. In the Cox’s multivariate analysis, lymph node metastases (RR 6.685; P < 0.001) and depth of invasion (RR 14.0; P = 0.013) were significant indicators for recurrence, and strong BAMBI expression (RR 2.26; P = 0.057) tended to be significant.
CONCLUSION: BAMBI was linked to a potentially aggressive tumor phenotype and predicted tumor recurrence and cancer-related death in CRC. BAMBI expression might be applicable in the routine clinical setting of CRC.
