Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
BMC Cancer. 2012 Aug 29;12:376. doi: 10.1186/1471-2407-12-376.
Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients.
BRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154).
BRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P < 0.001) and poor overall survival (OS, P < 0.001) in the training set; these results were validated in the testing set and overall patient population. Cox regression analysis demonstrated that low BRMS1 expression was an independent prognostic factor for DMFS and OS in NPC.
Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients.
乳腺癌转移抑制因子 1(BRMS1)是一种转移抑制基因。本研究旨在探讨 BRMS1 对鼻咽癌(NPC)转移的影响,并评估 BRMS1 在 NPC 患者中的预后意义。
采用定量逆转录聚合酶链反应和 Western blot 检测 NPC 细胞系中 BRMS1 的表达。使用稳定表达 BRMS1 的 NPC 细胞进行体外划痕愈合和侵袭实验以及体内小鼠异种移植实验。对 274 例石蜡包埋的 NPC 标本进行免疫组织化学染色,分为训练集(n=120)和测试集(n=154)。
BRMS1 在 NPC 细胞系中表达下调。BRMS1 的过表达显著逆转了 NPC 细胞的体外和体内转移表型。重要的是,低 BRMS1 表达与训练集中较差的远处无转移生存(DMFS,P<0.001)和总生存(OS,P<0.001)相关;这些结果在测试集和总体患者人群中得到了验证。Cox 回归分析表明,低 BRMS1 表达是 NPC 患者 DMFS 和 OS 的独立预后因素。
转移抑制因子 BRMS1 的低表达可能是 NPC 患者预后不良的独立预后因素。