The expression and prognostic significance of bcl-2-associated transcription factor 1 in rectal cancer following neoadjuvant therapy
The expression and prognostic significance of bcl-2-associated transcription factor 1 in rectal cancer following neoadjuvant therapy
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DOI：
10.1111/his.12780
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发表时间：
2016-03-01
期刊：
影响因子：
6.4
通讯作者：
Murray, Graeme I.
中科院分区：
文献类型：
--
作者：
Brown, Gordon T.;Cash, Beatriz;Murray, Graeme I.
目的bcl-2相关转录因子1（BCLAF 1）是一种与bcl-2相关蛋白结合的核蛋白，可诱导细胞凋亡和自噬。本研究的目的是探讨BCLAF 1的表达在一系列的直肠癌后新辅助治疗。方法和resultsImmunohistochemistry进行后新辅助治疗直肠癌组织芯片。其中包括直肠癌（n = 248）、淋巴结转移（n = 76）和非肿瘤性直肠粘膜样本（n = 73）。使用我们已经开发的针对BCLAF 1的单克隆抗体。非肿瘤性直肠上皮细胞在隐窝和表面上皮细胞中均显示BCLAF 1的核定位，而直肠癌细胞核和细胞质中均显示BCLAF 1表达。大多数直肠癌显示中等或强的核免疫反应，但显示弱的胞浆免疫反应。与非肿瘤性直肠粘膜相比，原发性直肠癌细胞质BCLAF 1表达增加（P = 0.008）。BCLAF 1核表达阴性和弱表达与预后不良相关[风险比（HR）0.502，95%可信区间（CI）0.269-0.939，（2）= 4.876，P = 0.027]。核BCLAF 1表达在多变量模型中是独立预后的（HR 0.431，95%CI 0.221-0.840，P = 0.013）。结论本研究表明，新辅助治疗后直肠癌细胞质BCLAF 1表达和核BCLAF 1表达均增加，核BCLAF 1表达阴性和弱表达与预后不良独立相关。
Aimsbcl-2-associated transcription factor 1 (BCLAF1) is a nuclear protein that binds to bcl-related proteins and can induce apoptosis and autophagy. The aim of this study was to investigate the expression of BCLAF1 in a series of rectal cancers following neoadjuvant therapy.Methods and resultsImmunohistochemistry was performed on a post-neoadjuvant therapy rectal cancer tissue microarray. It contained rectal cancers (n = 248), lymph node metastases (n = 76), and non-neoplastic rectal mucosal samples (n = 73). A monoclonal antibody against BCLAF1 that we have developed was used. Non-neoplastic rectal epithelium showed nuclear localization of BCLAF1 in both crypt and surface epithelial cells, whereas rectal cancers showed both nuclear and cytoplasmic BCLAF1 expression. Most rectal cancers showed moderate or strong nuclear immunoreactivity, but showed weak cytoplasmic immunoreactivity. Cytoplasmic BCLAF1 expression was increased in primary rectal cancers as compared with non-neoplastic rectal mucosa (P = 0.008). Negative and weak nuclear BCLAF1 expression was associated with a poor prognosis [hazard ratio (HR) 0.502, 95% confidence interval (CI) 0.269-0.939, (2) = 4.876, P = 0.027]. Nuclear BCLAF1 expression was independently prognostic in a multivariate model (HR 0.431, 95% CI 0.221-0.840, P = 0.013).ConclusionsThis study has shown that both cytoplasmic BCLAF1 expression and nuclear BCLAF1 expression are increased in post-neoadjuvant therapy rectal cancer, and that negative and weak nuclear BCLAF1 expression are independently associated with a poor prognosis.