Potential tumor suppressor NESG1 as an unfavorable prognosis factor in nasopharyngeal carcinoma.
Potential tumor suppressor NESG1 as an unfavorable prognosis factor in nasopharyngeal carcinoma.
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潜在的肿瘤抑制因子 NESG1 作为鼻咽癌的不良预后因素
DOI：
10.1371/journal.pone.0027887
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Fang W
中科院分区：
文献类型：
--
作者：
Liu Z;Luo W;Zhou Y;Zhen Y;Yang H;Yu X;Ye Y;Li X;Wang H;Jiang Q;Zhang Y;Yao K;Fang W
背景鼻咽上皮特异性蛋白1（NESG 1）是一种潜在的鼻咽癌抑癌基因。本研究的目的是探讨NESG 1在人NPC肿瘤进展和预后中的作用。方法/主要发现NESG 1蛋白在NPC中的表达进行了检查。采用Kaplan-Meier法进行生存分析。还研究了NESG 1对细胞增殖、迁移和侵袭的影响。结果NESG 1在鼻咽不典型增生和鼻咽癌组织中的表达明显低于正常鼻咽组织和鳞状细胞癌组织。蛋白表达降低与NPC进展状态呈负相关。与NESG 1高表达患者相比，NESG 1低表达患者的总生存期和无病时间较短。多因素分析提示NESG 1表达是鼻咽癌患者生存的独立预后指标。在慢病毒介导的NESG 1表达的shRNA抑制后，细胞系的增殖、迁移和侵袭能力显著增加。基因芯片分析表明NESG 1参与MAPK信号通路和细胞周期调控。最后，DNA甲基化微阵列检测显示NESG 1启动子缺乏高甲基化，表明其他机制参与了NPC中NESG 1表达的抑制。结论本研究首次证实NESG 1表达降低是影响鼻咽癌预后的一个不利因素。
Background Recently we identified nasopharyngeal epithelium specific protein 1 (NESG1) as a potential tumor suppressor in nasopharyngeal carcinoma (NPC). The purpose of this study is to investigate the involvement of NESG1 in tumor progression and prognosis of human NPC. Methodology/Principal Findings NESG1 protein expression in NPC was examined. Survival analysis was performed using Kaplan-Meier method. The effect of NESG1 on cell proliferation, migration, and invasion were also investigated. Results NESG1 expression was downregulated in atypical hyperplasia and NPC samples compared to normal and squamous nasopharynx tissues. Reduced protein expression was negatively associated with the status of NPC progression. Patients with lower NESG1 expression had a shorter overall survival and disease-free time than did patients with higher NESG1 expression. Multivariate analysis suggested NESG1 expression as an independent prognostic indicator for NPC patient survival. Proliferation, migration, and invasion ability were significantly increased in cell lines following lentiviral-mediated shRNA suppression of NESG1 expression. Microarray analysis indicated that NESG1 participated in multiple pathways, including MAPK signaling and cell cycle regulation. Finally, DNA methylation microarray examination revealed a lack of hypermethylation at the NESG1 promoter, suggesting other mechanisms are involved in suppressing NESG1 expression in NPC. Conclusion Our studies are the first to demonstrate that decreased NESG1 expression is an unfavorable prognostic factor for NPC.
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