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锌指蛋白X连锁的高表达与鼻咽癌中E-钙黏蛋白表达降低及不良预后相关。

High expression of Zinc-finger protein X-linked is associated with reduced E-cadherin expression and unfavorable prognosis in nasopharyngeal carcinoma.

作者信息

Li Yin, Yan Xuebing, Yan Leilei, Shan Zezhi, Liu Sihong, Chen Xiaojuan, Zou Jianyin, Zhang Weitian, Jin Zhiming

机构信息

Department of Otorhinolaryngology, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University 600 Yi-Shan Road, Shanghai 200233, China.

Department of Medicine, Soochow University 1 Shi-Zi Road, Suzhou 215006, China ; Department of General Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University 600 Yi-Shan Road, Shanghai 200233, China.

出版信息

Int J Clin Exp Pathol. 2015 Apr 1;8(4):3919-27. eCollection 2015.

Abstract

Zinc-finger protein X-linked (ZFX), a novel transcription factor required for self-renewal of embryonic stem cells, has recently been implicated in the initiation and progression of various human malignancies. However, its clinical significance in cancer patients remains largely inconclusive and its role in nasopharyngeal carcinoma (NPC) has never been reported. In this study, quantitative real-time polymerase chain reaction, Western blot and Immunohistochemistry were performed to detect ZFX expression in NPC and normal nasopharyngeal tissues. As a result, we found ZFX expression was significantly elevated in NPC tissues compared with that in normal nasopharyngeal tissues. The statistical analysis based on immunohistochemical staining demonstrated that ZFX expression was significantly correlated with lymph node stage and clinical stage. Furthermore, we found NPC patients with high ZFX expression had lower 5-year overall survival rates, progression-free survival rates, loco-regional relapse-free survival rates and distant metastasis-free survival rates than those with low ZFX expression (all P<0.05). The multivariate analysis indicated that ZFX expression was an independent prognostic factor for patients with NPC. More importantly, we also detected E-cadherin expression in NPC tissues and found it was inversely correlated with ZFX expression in NPC tissues, suggesting a potential involvement of ZFX in Epithelial-mesenchymal transition (EMT). Therefore, it is speculated that ZFX may promote NPC progression partly by regulating EMT. In summary, our study not only for the first time identified that ZFX could serve as an effective prognostic biomarker for NPC patients, but also suggested that targeting ZFX might be a novel therapeutic strategy for preventing NPC progression and metastasis.

摘要

锌指蛋白X连锁(ZFX)是胚胎干细胞自我更新所需的一种新型转录因子,最近被认为与多种人类恶性肿瘤的发生和发展有关。然而,其在癌症患者中的临床意义仍 largely inconclusive,且其在鼻咽癌(NPC)中的作用从未被报道过。在本研究中,采用定量实时聚合酶链反应、蛋白质免疫印迹法和免疫组织化学法检测NPC组织和正常鼻咽组织中ZFX的表达。结果发现,与正常鼻咽组织相比,NPC组织中ZFX的表达显著升高。基于免疫组织化学染色的统计分析表明,ZFX的表达与淋巴结分期和临床分期显著相关。此外,我们发现ZFX高表达的NPC患者的5年总生存率、无进展生存率、局部区域无复发生存率和远处转移无复发生存率均低于ZFX低表达的患者(所有P<0.05)。多因素分析表明,ZFX表达是NPC患者的独立预后因素。更重要的是,我们还检测了NPC组织中E-钙黏蛋白的表达,发现其与NPC组织中ZFX的表达呈负相关,提示ZFX可能参与上皮-间质转化(EMT)。因此,推测ZFX可能部分通过调节EMT促进NPC的进展。总之,我们的研究不仅首次确定ZFX可作为NPC患者有效的预后生物标志物,还提示靶向ZFX可能是预防NPC进展和转移的一种新的治疗策略。

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