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

Rui-Xue Cui,Na Liu,Ying Guo,Bi-Jun Huang,Hui-Yun Wang,Jun Ma,Mo Chen,Ying Sun,Qing-Mei He,Jing Zeng,Ling-Long Tang,Jing-Ping Yun,Lei Chen,Wen-Fei Li,Ning Jiang

doi:10.1186/1471-2407-12-376

Rui-Xue Cui, Na Liu + Show 13 more

Open Access

https://doi.org/10.1186/1471-2407-12-376

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Abstract

BackgroundBreast 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.MethodsBRMS1 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).ResultsBRMS1 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.ConclusionsLow expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients.

Highlights

Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene
BRMS1 expression is decreased in nasopharyngeal carcinoma (NPC) cells Since BRMS1 is a metastasis suppressor in many types of cancer, we hypothesize that NPC progression, especially NPC metastasis, may be related to BRMS1 levels
The results of quantitative reverse transcription-polymerase chain reaction and western blotting (Figure 1B) indicated that both BRMS1 mRNA and protein were markedly decreased in the examined NPC cell lines compared to the NP69, suggesting that low BRMS1 expression may be involved in NPC progression

Summary

Introduction

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. The breast cancer metastasis suppressor 1 (BRMS1) gene was originally identified as a true metastasis suppressor gene in breast cancer cell lines as stable overexpression of BRMS1 suppressed pulmonary metastasis but did not inhibit primary tumor growth [8]. Subsequent studies have demonstrated that BRMS1 dramatically suppresses the metastatic phenotype in vitro in cells from several othertypes of cancer, including melanoma [9,10], ovarian cancer [11], bladder cancer [12] and lung cancer [13]. BRMS1 was shown to inhibit metastasis in xenograft models of breast cancer [8], melanoma [9] and ovarian carcinoma [11].

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