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. 2022 Jul;11(7):2026-2039.
doi: 10.21037/tcr-22-372.

Association between eight hypermethylation-related genes and gastric cancer: a systematic review and meta-analysis

Chenhui Ma  1   2 , Bofang Wang  1 , Weigao Pu  1 , Huanhuan Ma  1 , Kewei Song  1 , Na Wang  1 , Xiaobo Deng  1 , Hao Chen  2   3
Affiliations

Association between eight hypermethylation-related genes and gastric cancer: a systematic review and meta-analysis

Chenhui Ma et al. Transl Cancer Res. 2022 Jul.

Abstract

Background: Although multiple gene promoter hypermethylation has been associated with gastric carcinogenesis, data on their specific relationship remains scant. We aimed to investigate the correlation between the status of multiple gene promoter methylation and gastric cancer (GC).

Methods: We searched PubMed, EMBASE, CNKI, Wanfang, Cqvip and Cochrane Library up to May 2021. We systematically assessed the association between methylation status of the CpG islands and the risk of GC. We compared the incidence of DNA methylation between tumor and non-tumor tissues, and evaluated the clinicopathological significance of the DNA methylation in gastric carcinoma. The data was presented by an odds ratio (OR) with an accompanying 95% confidence interval (CI). We then generated forest plots calculated by fixed-effects or random-effects model.

Results: This study enrolled a total of 201 studies (140 papers). Our analysis showed a higher frequency of methylation of the CpG islands in GC tissues compared to non-neoplastic tissues. Besides, the data demonstrated that polygene's aberrant promoter methylation might be linked to the initial development and progression of GC.

Discussion: The genes with altered DNA methylation might serve as epigenetic biomarkers, providing a promising molecular diagnostic and prognostic tool for human GC. However, our findings need further evaluation in large randomized controlled trials.

Keywords: DNA methylation; diagnosis; gastric cancer (GC); risk; tumor suppressor gene.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (Available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-372/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
DNA methylation process.
Figure 2
Figure 2
Shows the flow chart of the searches.
Figure 3
Figure 3
p16 promoter methylation and GC risk. (A) Forest plot for the association between p16 promoter methylation and GC risk; (B) funnel plot for the association between p16 promoter methylation and GC risk; (C) Egger’s publication bias plot for the association between p16 promoter methylation and GC risk. OR, odds ratio; CI, confidence interval; SE, standard error; GC, gastric cancer.
Figure 4
Figure 4
CDH1 promoter methylation and GC risk. (A) Forest plot for the association between CDH1 promoter methylation and GC risk; (B) funnel plot for the association between CDH1 promoter methylation and GC risk; (C) Egger’s publication bias for the association between CDH1 promoter methylation and GC risk. OR, odds ratio; CI, confidence interval; SE, standard error; GC, gastric cancer.
Figure 5
Figure 5
hMLH1 promoter methylation and GC risk. (A) Forest plot for the association between hMLH1 promoter methylation and GC risk; (B) funnel plot for the association between hMLH1 promoter methylation and GC risk; (C) Egger’s publication bias for the association between hMLH1 promoter methylation and GC risk. OR, odds ratio; CI, confidence interval; SE, standard error; ES, effect size; GC, gastric cancer.
Figure 6
Figure 6
RUNX3 promoter methylation and GC risk. (A) Forest plot for the association between RUNX3 promoter methylation and GC risk; (B) funnel plot for the association between RUNX3 promoter methylation and GC risk; (C) Egger’s publication bias plot for the association between RUNX3 promoter methylation and GC risk. OR, odds ratio; CI, confidence interval; SE, standard error; GC, gastric cancer.
Figure 7
Figure 7
RASSF1A promoter methylation and GC risk. (7A) Forest plot for the association between RASSF1A promoter methylation and GC risk; (B) funnel plot for the association between RASSF1A promoter methylation and GC risk; (C) Egger’s publication bias for the association between RASSF1A promoter methylation and GC risk. OR, odds ratio; CI, confidence interval; SE, standard error; ES, effect size; GC, gastric cancer.
Figure 8
Figure 8
MGMT promoter methylation and GC risk. (A) Forest plot for the association between MGMT promoter methylation and GC risk; (B) funnel plot for the association between MGMT promoter methylation and GC risk; (C) Egger’s publication bias for the association between MGMT promoter methylation and GC risk. OR, odds ratio; CI, confidence interval; SE, standard error; GC, gastric cancer.
Figure 9
Figure 9
DAPK promoter methylation and GC risk. (A) Forest plot for the association between DAPK promoter methylation and GC risk; (B) funnel plot for the association between DAPK promoter methylation and GC risk; (C) Egger’s publication bias for the association between DAPK promoter methylation and GC risk. OR, odds ratio; CI, confidence interval; SE, standard error; ES, effect size; GC, gastric cancer.
Figure 10
Figure 10
CHFR promoter methylation and GC risk; (A) Forest plot for the association between CHFR promoter methylation and GC risk; (B) funnel plot for the association between CHFR promoter methylation and GC risk; (C) Egger’s publication bias for the association between CHFR promoter methylation and GC risk. OR, odds ratio; CI, confidence interval; SE, standard error; ES, effect size; GC, gastric cancer.
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