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NDRG4基因高甲基化是中国人群胃癌诊断和预后的潜在生物标志物。

NDRG4 hypermethylation is a potential biomarker for diagnosis and prognosis of gastric cancer in Chinese population.

作者信息

Chen Xiaoying, Yang Yong, Liu Jing, Li Bin, Xu Yan, Li Cong, Xu Qi, Liu Guili, Chen Yingmin, Ying Jieer, Duan Shiwei

机构信息

Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.

Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.

出版信息

Oncotarget. 2017 Jan 31;8(5):8105-8119. doi: 10.18632/oncotarget.14099.

DOI:10.18632/oncotarget.14099
PMID:28042954
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5352386/
Abstract

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.

摘要

为了评估N-Myc下游调控基因4(NDRG4)甲基化与胃癌的诊断及预后是否相关,我们采用定量方法(甲基化特异性荧光定量PCR和焦磷酸测序)检测了110例胃癌患者中NDRG4启动子和基因体区域的甲基化情况。与配对的癌旁正常组织相比,肿瘤组织中NDRG4启动子和基因体的甲基化水平均升高(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启动子高甲基化被证明是总生存期较差的一个预测指标。然而,在癌症基因组图谱(TCGA)队列中观察到了相反的结果。来自胃癌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实验表明,启动子CpG岛而非基因体CpG岛能够上调基因表达。总体而言,NDRG4启动子高甲基化增加了胃癌风险,并预测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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ef/5352386/20e69206d0ff/oncotarget-08-8105-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ef/5352386/fd3d07fa3de6/oncotarget-08-8105-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ef/5352386/e2ab59b7e476/oncotarget-08-8105-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ef/5352386/20e69206d0ff/oncotarget-08-8105-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ef/5352386/fd3d07fa3de6/oncotarget-08-8105-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ef/5352386/d3dd6799e55d/oncotarget-08-8105-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ef/5352386/c23b4df83754/oncotarget-08-8105-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ef/5352386/e2ab59b7e476/oncotarget-08-8105-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20ef/5352386/20e69206d0ff/oncotarget-08-8105-g005.jpg

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