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.
Highlights
Cancer is a leading cause of death worldwide, accounting for 7.6 million deaths in 2008, and this number is projected to continue increasing to an estimated 13.1 million deaths in 2030 [1]
Our meta-analysis findings support the hypothesis that the global DNA hypomethylation is associated with a detrimental prognosis in tumour patients
CpGs are disproportionately concentrated in enriched regions referred to as CpG islands (CGIs), which tend to be differentially located in the promoter regions of genes, 70–90% of all CpGs in the human genome are in regions of large repetitive sequences and are typically methylated under normal conditions [5]
Summary
Cancer is a leading cause of death worldwide, accounting for 7.6 million deaths (approximately 13% of all deaths) in 2008, and this number is projected to continue increasing to an estimated 13.1 million deaths in 2030 [1]. CpGs are disproportionately concentrated in enriched regions referred to as CpG islands (CGIs), which tend to be differentially located in the promoter regions of genes, 70–90% of all CpGs in the human genome are in regions of large repetitive sequences (i.e. centromeres and retrotransposon elements) and are typically methylated under normal conditions [5]. With the recent developments in the high-throughput and highresolution methods for DNA methylation analysis such as pyrosequencing and luminometric methylation assays (LUMAs), global DNA methylation level was fully analysed in various tumours. Aberrant methylation of the global genome has been investigated as a prognostic indicator in various cancers, but the results are controversial and ambiguous
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