Togo Nozomi, Ohwada Susumu, Sakurai Shinji, Toya Hiroyuki, Sakamoto Ichiro, Yamada Tatsuya, Nakano Tetsuhiro, Muroya Ken, Takeyoshi Izumi, Nakajima Takashi, Sekiya Takashi, Yamazumi Yusuke, Nakamura Tsutomu, Akiyama Tetsu
Department of Surgery, Graduate School of Medicine, Gunma University, 3-39-22 Showa-Machi, Maebashi, Gunma, Japan.
World J Gastroenterol. 2008 Aug 21;14(31):4880-8. doi: 10.3748/wjg.14.4880.
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.
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.
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.
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.
研究骨形态发生蛋白和激活素膜结合抑制剂（BAMBI）的临床意义，BAMBI是转化生长因子-β（TGF-β）I型受体的假受体，作为TGF-β信号的负调节因子，在结直肠癌（CRC）中表达异常升高。我们研究了BAMBI在CRC中的表达。
我们使用生成的单克隆抗BAMBI抗体，通过免疫化学和免疫印迹分析研究了183例手术切除的CRC中BAMBI的表达。作为对照，还使用市售的抗β-连环蛋白和抗p53抗体进行免疫化学分析。
免疫组织化学分析显示，148例（80.8%）CRC中观察到BAMBI表达，46%的CRC中观察到强BAMBI表达。强BAMBI表达与组织学类型、浸润深度、淋巴结转移和肿瘤淋巴结转移（TNM）分期呈正相关（P<0.05）。发现BAMBI与β-连环蛋白（P=0.035）和p53（P=0.049）表达之间存在明显关联。在根治性切除的CRC中，强BAMBI表达的5年无复发生存率为51.9%（P=0.037），而弱BAMBI表达的为79.8%。在Cox多因素分析中，淋巴结转移（RR 6.685；P<0.001）和浸润深度（RR 14.0；P=0.013）是复发的重要指标，强BAMBI表达（RR 2.26；P=0.057）也趋于显著。
BAMBI与潜在的侵袭性肿瘤表型相关，可预测CRC中的肿瘤复发和癌症相关死亡。BAMBI表达可能适用于CRC的常规临床情况。
