Open Access Research article

Low BRMS1 expression promotes nasopharyngeal carcinoma metastasis in vitro and in vivo and is associated with poor patient survival

Rui-Xue Cui12, Na Liu12, Qing-Mei He2, Wen-Fei Li1, Bi-Jun Huang2, Ying Sun1, Ling-Long Tang1, Mo Chen1, Ning Jiang12, Lei Chen1, Jing-Ping Yun23, Jing Zeng23, Ying Guo4, Hui-Yun Wang2* and Jun Ma125*

Author Affiliations

1 Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China

2 Present address: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, Peoples Republic of China

3 Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Peoples Republic of China

4 Department of National Clinical Study Center for Anticancer Drugs, Sun Yat-sen University Cancer Center, Guangzhou, Peoples Republic of China

5 Department of Radiation Oncology State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Peoples Republic of China

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BMC Cancer 2012, 12:376  doi:10.1186/1471-2407-12-376

Published: 29 August 2012

Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients.

Keywords:
BRMS1; Nasopharyngeal carcinoma; Metastasis; Prognosis