The significance of ENAH in carcinogenesis and prognosis in gastric cancer.

The significance of ENAH in carcinogenesis and prognosis in gastric cancer.
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ENAH在胃癌发生及预后中的意义

DOI:
10.18632/oncotarget.19801
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发表时间:
2017-09-22
期刊:
影响因子:
--
通讯作者:
Shi B
Shi B
中科院分区:
其他
文献类型:
--
作者:
Wang DD;Jin Q;Wang LL;Han SF;Chen YB;Sun GD;Sun SF;Sun SW;Wang T;Liu FJ;Wang P;Shi B

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ENAH基因编码使能/血管舒张刺激磷蛋白(Ena/VASP)蛋白家族的成员,参与细胞粘附和运动所需的肌动蛋白丝的组装。最近的研究表明,在几种癌症类型中过表达ENAH,并且ENAH与肿瘤侵袭性相关。本研究旨在探讨ENAH在原发性胃腺癌组织中的表达、功能及其与预后的关系。胃癌组织中ENAH的mRNA(P = 0.0283)和蛋白(P = 0.0301)表达均显著增加。ENAH表达与肿瘤大小(P < 0.001)、T分期(P < 0.001)、N分期(P = 0.001)、TNM分期(P < 0.001)及预后(P < 0.001)有关。考克斯回归分析显示ENAH表达是总生存期的独立预测因子(P = 0.019)。我们还分析了155例胃癌患者的资料,发现ENAH表达与年龄(P = 0.003)、T分期(P = 0.023)和预后(P = 0.05)显著相关。体外实验分析ENAH在胃癌细胞增殖、集落形成、迁移和侵袭中的作用。在MKN 45细胞中,敲低ENAH表达抑制细胞增殖、集落形成、细胞迁移和侵袭。相反,ENAH的过表达促进了MGC 803细胞的增殖、迁移和侵袭。提示ENAH可能在胃癌的发生、发展过程中起促进作用,可作为胃癌患者的一个有价值的预后指标。
The ENAH gene, which encodes a member of the enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family of proteins, is involved in the assembly of actin filaments required for cell adhesion and motility. Recent studies show overexpressed ENAH in several cancer types, and ENAH correlates with tumor invasiveness. This study aimed to investigate the expression and function of ENAH in primary gastric adenocarcinoma, and its prognostic significance. We found significantly increased mRNA (P = 0.0283) and protein (P = 0.0301) expression of ENAH in gastric cancer tissues. ENAH expression markedly associated with tumor size (P < 0.001), T stage (P < 0.001), N stage (P = 0.001), TNM stage (P < 0.001) and prognosis (P < 0.001). Cox regression analyses revealed ENAH expression as an independent predictor of overall survival (P = 0.019). We also analyzed data of 155 gastric cancer cases from The Cancer Genome Atlas (TCGA) and found that ENAH expression significantly correlated with age (P = 0.003), T stage (P = 0.023) and prognosis (P = 0.05). Furthermore, the function of ENAH in cell proliferation, colony formation, cell migration and invasion of gastric cancer cells was analyzed in vitro. Knockdown of ENAH expression suppressed cell proliferation, colony formation, cell migration and invasion in MKN45 cells. Conversely, overexpression of ENAH promoted cell proliferation, cell migration and invasion in MGC803 cells. Our research suggests that ENAH might play promoting functions in carcinogenesis and progression of gastric cancer, and may serve as a valuable prognostic marker for primary gastric adenocarcinoma patients.
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