Clinical Potential of DNA Methylation in Gastric Cancer: A Meta-Analysis

Abstract

BackgroundAccumulating evidence indicates aberrant DNA methylation is involved in gastric tumourigenesis, suggesting it may be a useful clinical biomarker for the disease. The aim of this study was to consolidate and summarize published data on the potential of methylation in gastric cancer (GC) risk prediction, prognostication and prediction of treatment response.MethodsRelevant studies were identified from PubMed using a systematic search approach. Results were summarized by meta-analysis. Mantel-Haenszel odds ratios were computed for each methylation event assuming the random-effects model.ResultsA review of 589 retrieved publications identified 415 relevant articles, including 143 case-control studies on gene methylation of 142 individual genes in GC clinical samples. A total of 77 genes were significantly differentially methylated between tumour and normal gastric tissue from GC subjects, of which data on 62 was derived from single studies. Methylation of 15, 4 and 7 genes in normal gastric tissue, plasma and serum respectively was significantly different in frequency between GC and non-cancer subjects. A prognostic significance was reported for 18 genes and predictive significance was reported for p16 methylation, although many inconsistent findings were also observed. No bias due to assay, use of fixed tissue or CpG sites analysed was detected, however a slight bias towards publication of positive findings was observed.ConclusionsDNA methylation is a promising biomarker for GC risk prediction and prognostication. Further focused validation of candidate methylation markers in independent cohorts is required to develop its clinical potential.

DNA methylation status of a distinctively different subset of genes is associated with each histologic Lauren classification subtype in early gastric carcinogenesis

“…It is the fourth most common cancer and the second leading cause of cancer-related death worldwide (1)(2)(3). In Asian countries such as Japan and Korea, it has the highest incidence among all malignancies although its overall survival rate has improved during the last few decades due to extensive screening programs (3,4).…”

“…For this reason, aberrant DNA methylation is being highlighted as the main change differentiating these subtypes of GCs from the very first stage (1,11,12). Accumulating evidence from over 550 studies including the authors' previous study has demonstrated that aberrant epigenetic changes of more than 100 genes play a crucial role in the early steps of gastric carcinogenesis (2,13). However, the results of these studies were based only on a small portion of GCs and at times were conflicting in regards to a certain candidate gene.…”

“…However, the results of these studies were based only on a small portion of GCs and at times were conflicting in regards to a certain candidate gene. That may be because most studies reported to date have focused on the presence of epigenetic alterations and their prognostic value as a screening tool without accurate consideration of their possible linkage with histologic or phenotypic features, and the stage of carcinogenesis that is mainly involved (2). Furthermore, large scale screenings of epigenetic changes in GCs have been rarely performed.…”

DNA Damage-Inducible Gene, Reprimo Functions as a Tumor Suppressor and Is Suppressed by Promoter Methylation in Gastric Cancer

“…When methylation occurs within dinucleiotide CpG-rich regions, "CpG islands," of a gene promoter, it is associated with a compact chromatin structure and is accompanied by transcriptional silencing of the affiliated gene, especially tumor-suppressor genes (5). DNA methylation occurs more frequently than genetic mutations in gastric cancer and has recently opened the exciting doors for developing cancer biomarkers and therapeutic targets (6)(7)(8).…”

DNA hypermethylation and DNA hypomethylation is present at different loci in chronic kidney disease

“…Nonetheless, accumulating evidence suggests that DNA methylation differences are associated with complex disease and aggregated results from cross-center studies are revealing promising biomarkers. 72,73 The approach described in this manuscript carefully considered tissue type and cell heterogeneity, employed cost-effective 450K analysis for discovery at genome-wide significance, followed by verification and validation using an alternative approach to minimize experimental artifacts, and explored biological relevance alongside expression data for top-ranked markers. Following our identification of associated methylation changes with CKD, replication in additional cohorts is required to confirm these variants and ideally prospective studies would be performed to resolve the methylation influences of cause or effect.…”