NF-κB and Bcl-3 Activation Are Prognostic in Metastatic Colorectal Cancer
NF-κB and Bcl-3 Activation Are Prognostic in Metastatic Colorectal Cancer
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DOI：
10.1159/000313697
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发表时间：
2010-01-01
期刊：
影响因子：
3.5
通讯作者：
O'Neil, Bert H.
中科院分区：
文献类型：
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作者：
Puvvada, Soham D.;Funkhouser, William K.;O'Neil, Bert H.
目的：NF-κ B B是一种抗凋亡转录因子，已被证明是治疗抵抗的介导者。Bcl-3是NF-κ B B的调节因子，可能在肿瘤发生中起作用。本研究的目的是在一组转移性结直肠癌（CRC）患者中将NF-κ B和Bcl-3的活化状态与临床结果相关联。方法：回顾性研究了23例在北卡罗来纳州接受手术切除的结直肠癌患者。NF-κ B的活化通过NF-κ B的选择组分（p50、p52、p65）和Bcl-3的核表达来定义。组织微阵列由来自块的不同区域的正常粘膜、原发性肿瘤、淋巴结转移和肝转移的核心一式三份产生，并且通过将强度（0-3+）乘以阳性肿瘤细胞的百分比来产生强度评分。广义估计方程被用来说明正常粘膜和非正常组织之间的强度评分的差异。拟合考克斯回归模型以观察评分是否与总生存期显著相关。结果：p65 NE在原发灶和肝转移灶中的表达明显高于正常肝组织（P均< 0.01）。所有肿瘤部位的p50核表达均显著高于正常粘膜（原发肿瘤和淋巴结转移p < 0.0001，肝转移p < 0.01）。Bcl-3核表达在正常粘膜和肿瘤之间没有显著差异;然而，这些成分中的每一种在原发性肿瘤中的核表达与生存率密切相关：核表达每增加50点，风险增加Bcl-3为91%，p65为66%，p50为52%（所有p < 0.05）。结论：通过核表达测量的典型NF-κ B亚单位p50和p65的活化与存活率密切相关，表明NF-κ B是该疾病的预后因素。原发肿瘤核表达在预测预后方面似乎与转移部位一样好或更好。Bcl-3核表达也与生存率呈负相关，值得在CRC中进一步研究。版权所有（C）2010 S. Karger AG，巴塞尔
Purpose: NF-kappa B is an antiapoptotic transcription factor that has been shown to be a mediator of treatment resistance. Bcl-3 is a regulator of NF-kappa B that may play a role in oncogenesis. The goal of this study was to correlate the activation status of NF-kappa B and Bcl-3 with clinical outcome in a group of patients with metastatic colorectal cancer (CRC). Methods: A retrospective study of 23 patients who underwent surgical resection of CRC at the University of North Carolina (UNC). Activation of NF-kappa B was defined by nuclear expression of select components of NF-kappa B (p50, p52, p65) and Bcl-3. Tissue microarrays were created from cores of normal mucosa, primary tumor, lymph node metastases and liver metastases in triplicate from disparate areas of the blocks, and an intensity score was generated by multiplying intensity (0-3+) by percent of positive tumor cells. Generalized estimating equations were used to note differences in intensity scores among normal mucosa and nonnormal tissues. Cox regression models were fit to see if scores were significantly associated with overall survival. Results: p65 NE was significantly higher in primary tumor and liver metastases than normal mucosa (both p < 0.01). p50 nuclear expression was significantly higher for all tumor sites than for normal mucosa (primary tumor and lymph node metastases p < 0.0001, liver metastases p < 0.01). Bcl-3 nuclear expression did not differ significantly between normal mucosa and tumor; however, nuclear expression in primary tumor for each of these components was strongly associated with survival: the increase in hazard for each 50-point increase in nuclear expression was 91% for Bcl-3, 66% for p65, and 52% for p50 (all p < 0.05). Conclusions: Activation of canonical NF-kappa B subunits p50 and p65 as measured by nuclear expression is strongly associated with survival suggesting NF-kappa B as a prognostic factor in this disease. Primary tumor nuclear expression appears to be as good as, or better than, metastatic sites at predicting prognosis. Bcl-3 nuclear expression is also negatively associated with survival and deserves further study in CRC. Copyright (C) 2010 S. Karger AG, Basel