Prognostic significance of BMP and activin membrane-bound inhibitor in colorectal cancer

World J Gastroenterol. 2008 Aug 21;14(31):4880-8. doi: 10.3748/wjg.14.4880.

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-beta) type I receptors and acts as a negative regulator of TGF-beta 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-beta-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 beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Colorectal Neoplasms / chemistry*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Membrane Proteins / analysis*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Phenotype
  • Proportional Hazards Models
  • Risk Assessment
  • Time Factors
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / analysis
  • Up-Regulation
  • beta Catenin / analysis

Substances

  • BAMBI protein, human
  • Biomarkers, Tumor
  • CTNNB1 protein, human
  • Membrane Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta Catenin