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鼻咽癌患者血清中的Alu甲基化

Alu methylation in serum from patients with nasopharyngeal carcinoma.

作者信息

Tiwawech Danai, Srisuttee Ratakorn, Rattanatanyong Prakasit, Puttipanyalears Charoenchai, Kitkumthorn Nakarin, Mutirangura Apiwat

机构信息

Research Division, National Cancer Institute, Bangkok, Thailand E-mail :

出版信息

Asian Pac J Cancer Prev. 2014;15(22):9797-800. doi: 10.7314/apjcp.2014.15.22.9797.

DOI:10.7314/apjcp.2014.15.22.9797
PMID:25520107
Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast Asia. Alu elements are among the most prevalent repetitive sequences and constitute 11% of the human genome. Although Alu methylation has been evaluated in many types of cancer, few studies have examined the levels of this modification in serum from NPC patients.

OBJECTIVE

To compare the Alu methylation levels and patterns between serum from NPC patients and normal controls.

MATERIALS AND METHODS

Sera from 50 NPC patients and 140 controls were examined. Quantitative combined bisulfite restriction analysis-Alu (qCOBRA-Alu) was applied to measure Alu methylation levels and characterize Alu methylation patterns. Amplified products were classified into four patterns according to the methylation status of 2 CpG sites: hypermethylated (methylation at both loci), partially methylated (methylation of either of the two loci), and hypomethylated (unmethylated at both loci).

RESULTS

A comparison of normal control sera with NPC sera revealed that the latter presented a significantly lower methylation level (p=0.0002) and a significantly higher percentage of hypomethylated loci (p=0.0002). The sensitivity of the higher percentage of Alu hypomethyted loci for distinguishing NPC patients from normal controls was 96%.

CONCLUSIONS

Alu elements in the circulating DNA of NPC patients are hypomethylated. Moreover, Alu hypomethylated loci may represent a potential biomarker for NPC screening.

摘要

背景

鼻咽癌(NPC)是中国南方和东南亚地区常见的癌症。Alu元件是最普遍的重复序列之一,占人类基因组的11%。尽管在许多类型的癌症中都对Alu甲基化进行了评估,但很少有研究检测鼻咽癌患者血清中这种修饰的水平。

目的

比较鼻咽癌患者血清与正常对照血清中Alu甲基化水平和模式。

材料与方法

检测了50例鼻咽癌患者和140例对照的血清。应用定量联合亚硫酸氢盐限制性分析-Alu(qCOBRA-Alu)来测量Alu甲基化水平并表征Alu甲基化模式。根据2个CpG位点的甲基化状态,将扩增产物分为四种模式:高甲基化(两个位点均甲基化)、部分甲基化(两个位点中的任意一个甲基化)和低甲基化(两个位点均未甲基化)。

结果

正常对照血清与鼻咽癌血清的比较显示,后者的甲基化水平显著降低(p = 0.0002),低甲基化位点的百分比显著升高(p = 0.0002)。Alu低甲基化位点百分比升高用于区分鼻咽癌患者与正常对照的敏感性为96%。

结论

鼻咽癌患者循环DNA中的Alu元件发生低甲基化。此外,Alu低甲基化位点可能代表鼻咽癌筛查的潜在生物标志物。

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