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评估临床可行性:采用直接亚硫酸氢盐基因组测序法检测E3泛素连接酶RNF180 DNA启动子的甲基化状态以预测胃癌患者的生存期。

Evaluating the clinical feasibility: The direct bisulfite genomic sequencing for examination of methylated status of E3 ubiquitin ligase RNF180 DNA promoter to predict the survival of gastric cancer.

作者信息

Xie Xing-Ming, Deng Jing-Yu, Hou Ya-Chao, Cui Jing-Li, Wu Wei-Peng, Ying Guo-Guang, Dong Qiu-Ping, Hao Xi-Shan, Liang Han

机构信息

Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

Central Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

出版信息

Cancer Biomark. 2015;15(3):259-65. doi: 10.3233/CBM-150466.

DOI:10.3233/CBM-150466
PMID:25769451
Abstract

BACKGROUND

E3 ubiquitin ligase Ring finger protein 180 (RNF180) has been identified as a novel tumor suppressor in gastric cancer and the methylated CpG site count of RNF180 DNA promoter can predict the prognosis for gastric cancer patients.

OBJECTIVE

In the previous study, we demonstrated that methylated CpG site count of RNF180 DNA promoter was significantly associated with the survival of patients with gastric cancer using the bisulfite genomic sequencing (BGS) in the gastric cancer tissue with five clones per sample. It was so complicate for each patient underwent the BGS detection with clones. It is important to explore a simple, rapid and accurate method to detect methylated CpG site count to predicting the prognosis for gastric cancer patients.

METHODS

At present study, we detected hypermethylated and hypomethylated CpG site count of RNF180 DNA promoter in samples of 480 gastric cancer patients by direct bisulfite sequencing.

RESULTS

We found that patients who possessed seven or less hypermethylated CpG sites of RNF180 DNA promoter had much better survival (p= 0.008), which was similar to our previous research results by using the BGS with clones. With the multivariate survival analysis, we found that T stage, N stage and hypermethylated CpG site count of RNF180 DNA promoter were the independent predictors of prognosis for gastric cancer patients.

CONCLUSIONS

hypermethylated CpG site count of RNF180 DNA promoter for evaluating the prognosis of gastric cancer was reasonable by using the direct bisulfite sequencing.

摘要

背景

E3泛素连接酶环状指蛋白180(RNF180)已被确定为胃癌中的一种新型肿瘤抑制因子,RNF180 DNA启动子的甲基化CpG位点计数可预测胃癌患者的预后。

目的

在先前的研究中,我们使用亚硫酸氢盐基因组测序(BGS)对胃癌组织中每个样本有五个克隆的情况进行检测,结果表明RNF180 DNA启动子的甲基化CpG位点计数与胃癌患者的生存率显著相关。对每个患者进行带有克隆的BGS检测非常复杂。探索一种简单、快速且准确的检测甲基化CpG位点计数的方法以预测胃癌患者的预后很重要。

方法

在目前的研究中,我们通过直接亚硫酸氢盐测序检测了480例胃癌患者样本中RNF180 DNA启动子的高甲基化和低甲基化CpG位点计数。

结果

我们发现,RNF180 DNA启动子具有7个或更少高甲基化CpG位点的患者生存率要好得多(p = 0.008),这与我们之前使用带有克隆的BGS的研究结果相似。通过多因素生存分析,我们发现T分期、N分期和RNF180 DNA启动子的高甲基化CpG位点计数是胃癌患者预后的独立预测因素。

结论

使用直接亚硫酸氢盐测序通过RNF180 DNA启动子的高甲基化CpG位点计数来评估胃癌预后是合理的。

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