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Meta-Analysis
. 2017 Sep 19;12(9):e0184892.
doi: 10.1371/journal.pone.0184892. eCollection 2017.

Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer

Fatemeh Khatami  1 , Bagher Larijani  2 , Ramin Heshmat  1 , Abbasali Keshtkar  3 , Mahsa Mohammadamoli  2 , Ladan Teimoori-Toolabi  4 , Shirzad Nasiri  5 , Seyed Mohammad Tavangar  6
Affiliations
Meta-Analysis

Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer

Fatemeh Khatami et al. PLoS One. .

Abstract

Promoter methylation in a number of tumor-suppressor genes (TSGs) can play crucial roles in the development of thyroid carcinogenesis. The focus of the current meta-analysis was to determine the impact of promoter methylation of eight selected candidate TSGs on thyroid cancer and to identify the most important molecules in this carcinogenesis pathway. A comprehensive search was performed using Pub Med, Scopus, and ISI Web of Knowledge databases, and eligible studies were included. The methodological quality of the included studies was evaluated according to the Newcastle Ottawa scale table and pooled odds ratios (ORs); 95% confidence intervals (CIs) were used to estimate the strength of the associations with Stata 12.0 software. Egger's and Begg's tests were applied to detect publication bias, in addition to the "Metatrim" method. A total of 55 articles were selected, and 135 genes with altered promoter methylation were found. Finally, we included eight TSGs that were found in more than four studies (RASSF1, TSHR, PTEN, SLC5A, DAPK, P16, RARβ2, and CDH1). The order of the pooled ORs for these eight TSGs from more to less significant was CDH1 (OR = 6.73), SLC5 (OR = 6.15), RASSF1 (OR = 4.16), PTEN (OR = 3.61), DAPK (OR = 3.51), P16 (OR = 3.31), TSHR (OR = 2.93), and RARβ2 (OR = 1.50). Analyses of publication bias and sensitivity confirmed that there was very little bias. Thus, our findings showed that CDH1 and SCL5A8 genes were associated with the risk of thyroid tumor genesis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow diagram of study selection for the current meta-analysis.
Fig 2
Fig 2. The result of meta-analysis (random-effects model.
Forest plot for evaluating the association between promoter methylation in the eight tumor-suppressor genes (RASSF1, P16, TSHR, PTEN, NIS/SLC, DAPK, RARβ2, and CDH1) and thyroid cancer risk. For RASSF1 and NIS/SLC, subgroup analyses are also presented. The random-effect model was used for all analyses.
Fig 3
Fig 3. Funnel plot of publication bias.
Funnel plot for evaluating the association of promoter methylation of eight tumor-suppressor genes with thyroid cancer risk.
Fig 4
Fig 4. The result of Sensitivity analysis by the trim-and-fill method.
Funnel graph of the trim-and-fill method for evaluating publication bias and sensitivity for eight tumor-suppressor genes.
See this image and copyright information in PMC

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