A novel molecular marker for early detection and evaluating prognosis of gastric cancer: N-myc downstream regulated gene-1 (NDRG1)

A novel molecular marker for early detection and evaluating prognosis of gastric cancer: N-myc downstream regulated gene-1 (NDRG1)
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胃癌早期检测和预后评估的新型分子标志物:N-myc下游调节基因1(NDRG1)

DOI:
10.3109/00365520903242580
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发表时间:
2010-08-01
影响因子:
1.9
通讯作者:
Wang, Shan
Wang, Shan
中科院分区:
医学4区
文献类型:
--
作者:
Jiang, Kewei;Shen, Zhanlong;Wang, Shan

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抽象目标。N-myc下游调节基因1(NDRG 1)是一个分化相关基因,在细胞分化、器官形成和胚胎发育中起重要作用。最近发现NDRG 1在多种不同的肿瘤中显著下调。其在胃癌中的意义尚未研究。材料和方法。采用免疫组化法检测110对胃癌组织及癌旁组织中NDRG 1蛋白表达,采用真实的时间-聚合酶链反应(RT-PCR)检测NDRG 1 mRNA表达。同时观察NDRG 1与临床病理因素的相关性。通过细胞生长实验、凋亡实验、体外运动和侵袭实验检测NDRG 1过表达对胃癌细胞生物学行为的影响。结果NDRG 1蛋白在胃癌组织中表达下调,NDRG 1低表达率为73.6%(79/110)。NDRG 1的表达与肿瘤间质浸润、淋巴结转移、病理分期呈负相关,而与远处转移无关。NDRG 1低表达的患者的生存机会明显短于NDRG 1高表达的患者。NDRG 1过表达可诱导SGC 7901细胞早期凋亡,抑制SGC 7901细胞增殖、运动和侵袭能力。结论. NDRG 1在胃癌的发生、转移和侵袭中起重要作用。NDRG 1有可能成为胃癌诊断和预后评估的标志物,并可能成为胃癌治疗的潜在靶点。
Abstract Objective. N-myc downstream regulated gene-1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 was recently found to significantly down regulate in a variety of different neoplasms. Its significance in gastric cancer has not been studied. Materials and methods. NDRG1 was detected at its protein level by immunohistochemistry in formalin-fixed and paraffin-embedded sections with a total of 110 pair gastric cancer specimens including tumor and corresponding paraneoplastic tissues; NDRG1 mRNA was detected by real time-polymerase chain reaction. Meanwhile, the correlations between NDRG1 and clinicopathological factors were observed. Overexpression of NDRG1 has influence on the biological behavior of gastric cancer cell, which was detected by cell growth assay, apoptosis assay, and in vitro motility and invasion assay. Results. NDRG1 protein was down regulated in gastric cancer tissues, and the NDRG1 low expression rate was 73.6% (79/110). Moreover, NDRG1 expression has a significant inverse correlation with tumor stromal invasion, lymph node metastasis, pathological stage, but not with distant metastasis. The patients with low NDRG1 expression had a significantly shorter survival opportunity than those with high NDRG1 expression. In addition, overexpression of NDRG1 induced early apoptosis and inhibited SGC7901 cell proliferation and its motility and invasion capability. Conclusions. NDRG1 plays a significant role in carcinogenesis and preventing the metastasis and invasion of gastric cancer cells. NDRG1 could be developed as a marker contributing to diagnosis and evaluating prognosis in gastric cancer, as well as a potential therapeutic target of gastric cancer.