Association between TSHR gene methylation and papillary thyroid cancer: a meta-analysis

Purpose To explore the association between the thyroid stimulating hormone receptor (TSHR) gene methylation and human papillary thyroid cancer (PTC), as well as PTC related clinicopathological indicators. Methods We searched PubMed, Embase, Medline, and Web of Science databases through computer for articles published in English on association between methylation of TSHR gene and PTC. Articles published in Chinese were searched in China National Knowledge Infrastructure (CNKI), WanFang, China Biology Medicine (CBM) disc, and WeiPu databases. Database search took place in the 4th week of October. Results Totally 914 samples from 14 case-control studies were included in our meta-analysis. The methylation rate of TSHR gene in PTC group was significantly greater than that in control group (OR = 6.45, 95% CI 3.03, 13.71, P < 0.001). The subgroup analysis results showed the incidence of TSHR gene methylation was higher in autologous controls (OR = 16.39, 95% CI 8.83, 30.42, P < 0.001), Asian races (OR = 8.26, 95% CI 3.54, 19.23, P < 0.001), and Chinese (OR = 11.40, 95% CI 5.56, 23.39, P < 0.001). Hierarchical analysis of PTC related clinicopathological indicators showed that TSHR gene methylation rate are higher in PTC patients over 45 years (OR = 1.65, 95% CI 1.07, 2.55, P < 0.05) and lymph node metastasis (OR = 5.36, 95% CI 1.54, 18.67, P < 0.01). In addition, the occurrence of TSHR gene methylation had also been shown to be related to the clinical stage (OR = 0.23, 95% CI 0.07, 0.70, P < 0.05) and size (OR = 0.19, 95% CI 0.11, 0.32, P < 0.01) of tumors. The result of sensitivity analysis showed the combined results of the studies included in the meta-analysis were fairly stable. Begg's and Egger's tests also suggested that there was no significance publication bias (P > 0.1). Conclusions The rate of TSHR gene methylation is higher in PTC and it may be associated with the pathogenesis of human PTC, suggesting that TSHR gene may be a candidate marker for PTC diagnosis. In addition, the occurrence of TSHR gene methylation in PTC patients is closely related to age, lymph node metastasis, clinical stage, and tumor size, suggesting that TSHR gene may be used as an index to judge the severity of PTC.