LINE-1 hypomethylation in blood and tissue samples as an epigenetic marker for cancer risk: a systematic review and meta-analysis.

LINE-1 hypomethylation in blood and tissue samples as an epigenetic marker for cancer risk: a systematic review and meta-analysis.
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DOI:
10.1371/journal.pone.0109478
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Agodi A
Agodi A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Barchitta M;Quattrocchi A;Maugeri A;Vinciguerra M;Agodi A

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进行了系统综述和荟萃分析,以总结当前已发表的研究,并评估血液和其他组织中LINE-1低甲基化作为癌症风险的表观遗传标记。使用PubMed在Medline数据库中对2014年3月之前发表的流行病学研究进行了系统性文献检索。使用随机效应模型估计加权平均差异(MD)和95%置信区间(CI)。此外,通过样品类型(组织或血液样品)、癌症类型和用于测量总体DNA甲基化水平的测定进行亚组分析。使用了科克伦软件包Review Manager 5.2。荟萃分析共纳入了19篇关于6107份样本(2554份来自癌症患者,3553份对照样本)的独特文章。癌症患者的LINE-1甲基化水平显著低于对照组(MD:−6.40,95% CI:−7.71,−5.09; p<0.001)。在组织样本中证实了甲基化水平的显著差异(MD-7.55; 95% CI:-9.14,-65.95; p<0.001),但在血液样本中没有(MD:-0.26,95% CI:-0.69,0.17; p = 0.23)。  结直肠癌和胃癌患者的LINE-1甲基化水平显着低于对照组(MD:-8.33; 95%CI:-10.56,-6.10; p<0.001和MD:-5.75; 95%CI:-7.75,-3.74; p<0.001),而肝细胞癌患者则无显着差异。目前的荟萃分析为越来越多的关于LINE-1低甲基化在人类癌症中的作用的文献增加了新的证据,并证明癌症患者的LINE-1甲基化水平显著低于对照样本,特别是在某些癌症类型中。该结果在新鲜/冷冻或FFPE标本的组织样本中得到证实,但在血液中未得到证实。需要进一步的研究来更好地阐明LINE-1甲基化在特定亚组中的作用,同时考虑癌症和样本类型以及测量方法。
A systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other tissues as an epigenetic marker for cancer risk. A systematic literature search in the Medline database, using PubMed, was conducted for epidemiological studies, published before March 2014. The random-effects model was used to estimate weighted mean differences (MDs) with 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by sample type (tissue or blood samples), cancer types, and by assays used to measure global DNA methylation levels. The Cochrane software package Review Manager 5.2 was used. A total of 19 unique articles on 6107 samples (2554 from cancer patients and 3553 control samples) were included in the meta-analysis. LINE-1 methylation levels were significantly lower in cancer patients than in controls (MD: −6.40, 95% CI: −7.71, −5.09; p<0.001). The significant difference in methylation levels was confirmed in tissue samples (MD −7.55; 95% CI: −9.14, −65.95; p<0.001), but not in blood samples (MD: −0.26, 95% CI: −0.69, 0.17; p = 0.23). LINE-1 methylation levels were significantly lower in colorectal and gastric cancer patients than in controls (MD: −8.33; 95% CI: −10.56, −6.10; p<0.001 and MD: −5.75; 95% CI: −7.75, −3.74; p<0.001) whereas, no significant difference was observed for hepatocellular cancer. The present meta-analysis adds new evidence to the growing literature on the role of LINE-1 hypomethylation in human cancer and demonstrates that LINE-1 methylation levels were significantly lower in cancer patients than in control samples, especially in certain cancer types. This result was confirmed in tissue samples, both fresh/frozen or FFPE specimens, but not in blood. Further studies are needed to better clarify the role of LINE-1 methylation in specific subgroups, considering both cancer and sample type, and the methods of measurement.
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