Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer
Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer
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DOI：
10.1158/1078-0432.ccr-03-0489
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发表时间：
2004-07-01
影响因子：
11.5
通讯作者：
Jen, J
中科院分区：
文献类型：
--
作者：
Fukuoka, J;Fujii, T;Jen, J
我们使用由150例肺腺癌（AD）和150例鳞状细胞癌（SCC）病例组成的组织微阵列，用免疫组织化学方法检测了12种参与染色质重塑机制的核心蛋白。大多数蛋白质显示核染色，而一些也显示细胞质或膜染色。当考虑所有测试抗原的表达模式时，具有核染色的蛋白质聚簇成两个主要组。BRM、Ini-1、视网膜母细胞瘤、mSin 3A、HDAC 1和HAT 1的核信号聚集在一起，而BRG 1、BAF 155、HDAC 2、BAF 170和RbAP 48的核信号形成第二个簇。此外，肺组织阵列上三分之二的病例有随访信息，并对每种测试蛋白进行了生存分析。核BRM（N-BRM）染色阳性与SCC和AD患者的良好预后相关，5年生存率为53.5%，而N-BRM阴性患者的5年生存率为32.3%（P = 0.015）。此外，肿瘤N-BRM和核BRG 1染色阳性的患者的5年生存率为72%，而肿瘤两种标记物均阳性或阴性的患者的5年生存率为33.6%（P = 0.013）。相比之下，膜性BRM（M-BRM）染色与AD患者的预后较差相关，5年生存率为16.7%，与无M-BRM染色的患者相比（38.1%; P = 0.016）。这些结果支持BRM和BRG 1参与两种功能互补的不同染色体重塑复合物的概念，并且BRM的核存在、其与核BRG 1的共表达以及BRM的改变的细胞定位（M-BRM）是非小细胞肺癌预后的有用标志物。
We immunohistochemically examined 12 core proteins involved in the chromatin remodeling machinery using a tissue microarray composed of 150 lung adenocarcinoma (AD) and 150 squamous cell carcinoma (SCC) cases. Most of the proteins showed nuclear staining, whereas some also showed cytoplasmic or membranous staining. When the expression patterns of all tested antigens were considered, proteins with nuclear staining clustered into two major groups. Nuclear signals of BRM, Ini-1, retinoblastoma, mSin3A, HDAC1, and HAT1 clustered together, whereas nuclear signals of BRG1, BAF155, HDAC2, BAF170, and RbAP48 formed a second cluster. Additionally, two thirds of the cases on the lung tissue array had follow-up information, and survival analysis was performed for each of the tested proteins. Positive nuclear BRM (N-BRM) staining correlated with a favorable prognosis in SCC and AD patients with a 5 year-survival of 53.5% compared with 32.3% for those whose tumors were negative for N-BRM (P = 0.015). Furthermore, patients whose tumors stained positive for both N-BRM and nuclear BRG1 had a 5 year-survival of 72% compared with 33.6% (P = 0.013) for those whose tumors were positive for either or negative for both markers. In contrast, membranous BRM (M-BRM) staining correlated with a poorer prognosis in AD patients with a 5 year-survival of 16.7% compared with those without M-BRM staining (38.1%; P = 0.016). These results support the notion that BRM and BRG1 participate in two distinct chromosome remodeling complexes that are functionally complementary and that the nuclear presence of BRM, its coexpression with nuclear BRG1, and the altered cellular localization of BRM (M-BRM) are useful markers for non-small cell lung cancer prognosis.