NDRG4 hypermethylation is a potential biomarker for diagnosis and prognosis of gastric cancer in Chinese population.
NDRG4 hypermethylation is a potential biomarker for diagnosis and prognosis of gastric cancer in Chinese population.
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DOI：
10.18632/oncotarget.14099
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发表时间：
2017-01-31
期刊：
影响因子：
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通讯作者：
Duan S
中科院分区：
文献类型：
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作者：
Chen X;Yang Y;Liu J;Li B;Xu Y;Li C;Xu Q;Liu G;Chen Y;Ying J;Duan S
为了评估N-Myc下游调控基因4 （NDRG4）甲基化是否与胃癌的诊断和预后相关，我们采用定量方法（MethyLight和焦磷酸测序）测量了110例胃癌患者NDRG4启动子和基因体区的甲基化。肿瘤组织中NDRG4启动子和基因体甲基化水平均高于配对的邻近正常组织（P < 0.001）。发现NDRG4基因体甲基化与年龄和肿瘤分化显著相关。NDRG4启动子超甲基化被证明是总生存率较差的一个预测因子。然而，在癌症基因组图谱（TCGA）队列中观察到相反的结果。来自胃细胞系和公共数据库的研究结果表明，NDRG4甲基化水平与NDRG4转录水平呈负相关。随后的荧光素酶报告基因分析表明，启动子CpG岛而非基因体CpG岛能够上调基因的表达。综上所述，NDRG4启动子高甲基化增加了胃癌的风险，并预示着中国胃癌患者预后不良。此外，NDRG4启动子和基因体的联合甲基化水平可作为胃癌的诊断生物标志物。
In order to assess whether N-Myc downstream regulated gene 4 (NDRG4) methylation was associated with the diagnosis and prognosis of gastric cancer, we measured the methylation of NDRG4 promoter and gene body regions among 110 gastric cancer patients using quantitative methods (MethyLight and pyrosequencing). Both NDRG4 promoter and gene body methylation levels were increased in tumor tissues than paired adjacent normal tissues (P < 0.001). NDRG4 gene body methylation was found to be significantly associated with age and tumor differentiation. NDRG4 promoter hypermethylation was proved to be a predictor of poor overall survival. However, opposite result was observed among The Cancer Genome Atlas (TCGA) cohort. The findings from gastric cell lines and public databases have suggested that NDRG4 methylation level was inversely associated with NDRG4 transcription level. Subsequent luciferase reporter gene assay showed that promoter CpG island but not gene body CpG island was able to upregulate gene expression. Collectively, NDRG4 promoter hypermethylation contributed to the risk of gastric cancer and predicted a poor prognosis in Chinese gastric cancer patients. Moreover, the combined methylation levels of NDRG4 promoter and gene body served as diagnostic biomarkers in gastric cancer.