The Prognostic Value of Global DNA Hypomethylation in Cancer: A Meta-Analysis

Abstract

BackgroundAberrant methylation of the global genome has been investigated as a prognostic indicator in various cancers, but the results are controversial and ambiguous.Methods and FindingsThis meta-analysis presents pooled estimates of the evidence to elucidate this issue. We searched the electronic databases: PubMed, Embase, ISI Web of Science and the Cochrane library (up to August 2013) to identify all of the relevant studies. The association between the level of surrogates' indexes of genome-wide hypomethylation (LINE-1, Alu and Sat–α) and the overall survival (OS) of cancer patients was examined. In addition, the pooled hazard ratios (HRs) with their 95% confidence interval (95%CI) were calculated to estimate the influences through fixed-effects and random-effects model. Finally, twenty studies with total population of 5447 met the inclusion criteria. The results indicate that the summary HRs for the studies employing LINE-1, Alu, and Sat-α repetitive elements also show that the global DNA hypomethylation have significant desirable effects on the tumour prognostic value. The pooled HRs (and CIs) of LINE-1, Alu and Sat-α were 1.83 (1.38–2.44), 2.00 (1.16–3.45), and 2.92 (1.04–8.25), with a heterogeneity measure index of I2 (and p-value) shows of 66.6% (p = 0.001), 57.1% (p = 0.053) and 68.2% (p = 0.076) respectively. The meta-regression and subgroup analysis indicated that the percentage of hypomethylated sample of cancer patients is one source of heterogeneity.ConclusionOur meta-analysis findings support the hypothesis that the global DNA hypomethylation is associated with a detrimental prognosis in tumour patients.

Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children

“…Their high rates of methylation are likely responsible for the suppression of their transposition activity and thus lower levels of methylation of Alu and LINE-1 may lead to genomic instability (Xiao-Jie et al, 2015). Lower levels of methylation of LINE-1 and Alu elements has been associated with several cancers (Barchitta et al, 2014; Li et al, 2014; Salas et al, 2014) as well as some phthalate-related health outcomes such as obesity and sperm quality (Perng et al, 2013; Tian et al, 2014). However, it remains unclear how differences in DNA methylation of repetitive elements associated with prenatal phthalate exposures lead to health effects.…”

LINE‐1 hypomethylation induced by reactive oxygen species is mediated via depletion of S‐adenosylmethionine

“…Genome‐wide hypomethylation (also known as global hypomethylation) is commonly found in cancer genome, and it consequently causes genomic instability, aberrant transcription and mobilization of retrotransposons . Furthermore, global hypomethylation is associated with poor prognosis in cancer patients . Long interspersed nuclear element‐1 (LINE‐1) is a repetitive retrotransposon comprising about 18% of human genome (approx.…”

Global changes of 5-hydroxymethylcytosine and 5-methylcytosine from normal to tumor tissues are associated with carcinogenesis and prognosis in colorectal cancer

“…Some studies have shown that the Line-1 (long interspersed nuclear element 1) methylation level, which may represent global methylation status, is negatively associated with T-stage and is significantly reduced in lymph node metastases in CRC (Sunami et al, 2011;Morikawa et al, 2012). Furthermore, early studies found that 5mC is an independent marker of poor survival outcome in CRC patients (Frigola et al, 2005;Ogino et al, 2008;Li et al, 2014). However, there are few studies analyzing the relationship between clinicopathological features and the degree of change in 5mC from normal to tumor tissues in CRC patients.…”