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

An actin-binding protein ESPN is an independent prognosticator and regulates cell growth for esophageal squamous cell carcinoma
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DOI:
10.1186/s12935-018-0713-x
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发表时间:
2018-12-29
影响因子:
5.8
通讯作者:
Chen, Chang-Han
Chen, Chang-Han
中科院分区:
医学2区
文献类型:
--
作者:
Li, Shau-Hsuan;Lu, Hung-I;Chen, Chang-Han

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Espin (despn)是一种肌动蛋白结合蛋白,在调节肌动蛋白丝丰富的微绒毛型特化的组织、尺寸、动力学和信号能力方面发挥重要作用,介导各种机械感觉和化学感觉细胞的感觉转导。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))中的意义在很大程度上仍然未知。方法对169例ESCC患者进行免疫组化检查,并与临床病理特征及生存期进行比较。ESPN在ESCC细胞中的功能作用是通过ESPN介导的siRNA确定的。结果单因素分析显示,ESPN高表达与总生存期(P=0.005)和无病生存期(P=0.035)相关。在多变量分析中,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)的独立预后因素。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细胞的内源性ESPN通过降低细胞增殖率来降低ESCC的生长。结论ESPN高表达与ESCC患者预后不良独立相关,ESPN下调可抑制ESCC细胞生长。我们的研究结果表明,ESPN可能是ESCC患者的一个新的治疗靶点。
BackgroundESPN (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.MethodsImmunohistochemistry 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.ResultsUnivariate 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.ConclusionsHigh 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.