NDRG4 in gastric cancer determines tumor cell proliferation and clinical outcome

NDRG4 in gastric cancer determines tumor cell proliferation and clinical outcome
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胃癌中的 NDRG4 决定肿瘤细胞增殖和临床结果

DOI:
10.1002/mc.22798
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发表时间:
2018-06
影响因子:
4.6
通讯作者:
Chu Dake
Chu Dake
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Zixi;She Junjun;Yang Jingyi;Bu Xin;Ji Gang;Zhu Shaojun;He Shuixiang;Chu Dake

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作为一种新的候选抑癌基因,NDRG4在人类恶性肿瘤中的研究还很少。本研究旨在探讨NDRG4在胃癌组织中的表达水平及其与患者预后的关系。本研究以286例胃癌患者为研究对象,采用免疫组织化学方法和实时荧光定量聚合酶链式反应(Real-Time-PCR)检测了NDRG4在癌组织和癌旁正常组织中的蛋白和mRNA表达。通过适当的统计分析,研究NDRG4水平与临床病理特征的关系。为了检测NDRG4对细胞增殖和凋亡的影响,建立了NDRG4过表达和基因敲除细胞系。与癌旁正常组织相比,胃癌组织中NDRG4蛋白和mRNA的表达均显著降低。此外,研究还发现NDRG4蛋白在胃癌组织中的表达与肿瘤分化程度、侵袭、转移和分期密切相关。在单因素和多因素分析中,NDRG4水平降低的肿瘤患者更有可能有不良的无病生存和总体生存。此外,过表达NDRG4抑制了体外培养的胃癌细胞的增殖;反之,过表达NDRG4则促进了胃癌细胞的增殖。这些结果首次证明NDRG4可能是一种潜在的抑癌基因和预测胃癌预后的标志物。
As a novel candidate tumor suppressor, NDRG4 is largely unstudied in human malignancies. In this study, we investigated the protein expression level of NDRG4 in gastric cancer and its association with outcome of patients. In the present study, we recruited 286 patients with gastric cancer and investigated the protein and mRNA expression of NDRG4 in cancer and adjacent normal specimens by immunohistochemistry assay and real‐time PCR. The association of NDRG4 level with clinicopathological characteristics was investigated by appropriate statistical analysis. NDRG4 overexpression and knockdown cell lines were established in order to detect its impact on proliferation and apoptosis. Significant decreased protein and mRNA expression of NDRG4 was found in gastric cancer, compared with adjacent normal specimens. Besides, it was found that NDRG4 protein expression in gastric cancer was significantly associated with tumor differentiation, invasion, metastasis, and stage. Patients with tumors of decreased NDRG4 level were more likely to have unfavorable disease‐free and overall survival, in both univariate and multivariate analysis. In addition, overexpression of NDRG4 suppressed cell proliferation of gastric cancer cells in vitro; conversely, the proliferation of gastric cancer cells were enhanced by knockdown of NDRG4. These results proved for the first time that NDRG4 could be a potential tumor suppressor and prognostic marker of gastric cancer.
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