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一种肌动蛋白结合蛋白ESPN是一种独立的预后指标,并调节食管鳞状细胞癌的细胞生长。

An actin-binding protein ESPN is an independent prognosticator and regulates cell growth for esophageal squamous cell carcinoma.

作者信息

Li Shau-Hsuan, Lu Hung-I, Huang Wan-Ting, Chen Yen-Hao, Lo Chien-Ming, Lan Ya-Chun, Lin Wei-Che, Tsai Hsin-Ting, Chen Chang-Han

机构信息

Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.

Department of Thoracic & Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.

出版信息

Cancer Cell Int. 2018 Dec 29;18:219. doi: 10.1186/s12935-018-0713-x. eCollection 2018.

Abstract

BACKGROUND

ESPN (Espin), an actin filament-binding protein, plays an important role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Recent few studies show that ESPN regulates metastasis and cell proliferation in melanoma. However, the significance of ESPN in other cancers such as esophageal squamous cell carcinoma (ESCC) remains largely unknown.

METHODS

Immunohistochemistry was performed in 169 patients with ESCC and correlated with clinicopathological features and survival. The functional role of ESPN in ESCC cells was determined by ESPN-mediated siRNA.

RESULTS

Univariate analyses showed that high ESPN expression was associated with inferior overall survival (P = 0.005) and disease-free survival (P = 0.035). High ESPN expression was an independent prognosticator in multivariate analysis for overall survival (P = 0.009, hazard ratio = 1.688) and disease-free survival (P = 0.049, hazard ratio = 1.451). The 5-year overall survival rates were 30% and 54% in patients with high and low expression of ESPN, respectively. Inhibition of endogenous ESPN in ESCC cells decreased ESCC growth by reducing cell proliferating rates.

CONCLUSIONS

High ESPN expression is independently associated with poor prognosis in patients with ESCC and downregulation of ESPN inhibits ESCC cell growth. Our results suggest that ESPN may be a novel therapeutic target for patients with ESCC.

摘要

背景

ESPN(肌动蛋白丝结合蛋白)在调节富含肌动蛋白丝的微绒毛型特化结构的组织、尺寸、动力学和信号传导能力方面发挥着重要作用,这些特化结构介导各种机械感觉和化学感觉细胞中的感觉转导。最近的一些研究表明,ESPN调节黑色素瘤的转移和细胞增殖。然而,ESPN在其他癌症如食管鳞状细胞癌(ESCC)中的意义仍 largely未知。

方法

对169例ESCC患者进行免疫组织化学检测,并与临床病理特征和生存率相关联。通过ESPN介导的小干扰RNA确定ESPN在ESCC细胞中的功能作用。

结果

单因素分析显示,ESPN高表达与较差的总生存率(P = 0.005)和无病生存率(P = 0.035)相关。在多因素分析中,ESPN高表达是总生存率(P = 0.009,风险比 = 1.688)和无病生存率(P = 0.049,风险比 = 1.451)的独立预后指标。ESPN高表达和低表达患者的5年总生存率分别为30%和54%。抑制ESCC细胞中的内源性ESPN可通过降低细胞增殖率来减少ESCC生长。

结论

ESPN高表达与ESCC患者的不良预后独立相关,ESPN的下调抑制ESCC细胞生长。我们的结果表明,ESPN可能是ESCC患者的一个新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6497/6310995/b2186c60e158/12935_2018_713_Fig1_HTML.jpg

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