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Dapper同源物1(DACT1)启动子的甲基化CpG位点计数预示着胃癌患者的预后不良。

Methylated CpG site count of dapper homolog 1 (DACT1) promoter prediction the poor survival of gastric cancer.

作者信息

Deng Jingyu, Liang Han, Zhang Rupeng, Ying Guoguang, Xie Xingmin, Yu Jun, Fan Daiming, Hao Xishan

机构信息

Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer Tianjin, China.

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

出版信息

Am J Cancer Res. 2014 Sep 6;4(5):518-27. eCollection 2014.

Abstract

OBJECTIVE

To elucidate the clinical significance of the methylated status of CpG sites of dapper homolog 1 (DACT1) promoter in the survival prediction in gastric cancer (GC).

METHODS

The large scale GC patients (n=459) were analyzed for the quantitatively methylated status of CpG sites of DACT1 DNA promoter with the bisulphite sequencing PCR (BSP). With gene sequencing analysis, the methylated statuses of 12 cytosine-phosphate-guanine (CpG) sites in DACT1 promoter were detected to supply detailed information for the precisely prognostic prediction. Associations between molecular, clinicopathologic, and survival data were analyzed.

RESULTS

With the MSP detection, different methylated levels of DACT1 promoter were identified in the 25 GC tissues, while none of 25 normal gastric mucosal tissues were found to be methylated. DACT1 promoter methylation was found in 28.32% in 459 patients. GC patients with 4 or more methylated CpG sites of DACT1 promoter was significantly associated with the poorer survival (P=0.19). The methylated statuses of CpG -515, CpG -435, and CpG -430 sites were also identified to provide the elaborate survival discrimination for 459 GC patients, respectively (P=0.049, =0.006, and =0.037). In addition, we demonstrated that the methylated CpG site count had smallest AIC and BIC values than other three methylated status of CpG sites for prediction the survival of 459 GC patients.

CONCLUSIONS

The methylated CpG site count of DACT1 promoter had the significant applicability for clinical evaluation the prognosis of GC.

摘要

目的

阐明胃癌(GC)中dapper同源物1(DACT1)启动子CpG位点甲基化状态在生存预测中的临床意义。

方法

采用亚硫酸氢盐测序PCR(BSP)分析459例GC患者DACT1 DNA启动子CpG位点的定量甲基化状态。通过基因测序分析,检测DACT1启动子中12个胞嘧啶-磷酸-鸟嘌呤(CpG)位点的甲基化状态,为精确的预后预测提供详细信息。分析分子、临床病理和生存数据之间的关联。

结果

通过甲基化特异性PCR(MSP)检测,在25例GC组织中鉴定出不同甲基化水平的DACT1启动子,而25例正常胃黏膜组织均未发现甲基化。459例患者中DACT1启动子甲基化率为28.32%。DACT1启动子有4个或更多甲基化CpG位点的GC患者生存较差(P = 0.19)。还确定了CpG -515、CpG -435和CpG -430位点的甲基化状态,分别为459例GC患者提供了精细的生存判别(P = 0.049、= 0.006和= 0.037)。此外,我们证明,对于预测459例GC患者的生存,甲基化CpG位点计数的AIC和BIC值比其他三种CpG位点甲基化状态最小。

结论

DACT1启动子的甲基化CpG位点计数对GC预后的临床评估具有重要适用性。

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