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

Association between TSHR gene methylation and papillary thyroid cancer: a meta-analysis
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TSHR 基因甲基化与甲状腺乳头状癌之间的关联:荟萃分析

DOI:
10.1007/s12020-020-02284-7
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发表时间:
2020-04-11
期刊:
影响因子:
3.7
通讯作者:
Shen, Hongmei
Shen, Hongmei
中科院分区:
医学3区
文献类型:
--
作者:
Qu, Mengying;Wan, Siyuan;Shen, Hongmei

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目的探讨促甲状腺激素受体(TSHR)基因甲基化与人乳头状甲状腺癌(PTC)及其相关临床病理指标的关系。方法计算机检索PubMed、Embase、Medline、Web of Science等数据库,并限定文章语言种类为English。应用计算机检索中国国家知识基础设施、万方、中国生物医学(CBM)光盘和魏普数据库的文章,检索词为中文。结果14个病例对照研究共914个样本进入Meta分析。PTC组Tshr基因甲基化率显著高于对照组(OR = 6.45,95%CI 3.03,13.71,P< 0.001)。亚组分析结果显示,自身对照(OR = 16.39,95%CI 8.83,30.42,P< 0.001)、亚洲种族(OR = 8.26,95%CI 3.54,19.23,P< 0.001)和中国人(OR = 11.40,95%CI 5.56,23.39,P< 0.001)中TsHR基因甲基化的发生率较高。对PTC相关临床病理指标的分层分析显示,45岁以上(OR = 1.6 5,95%CI 1.0 7,2.5 5,P< 0.0 5)和有淋巴结转移(OR = 5.36,95%CI 1.5 4,18.67,P< 0.0 1)的PTC患者TsHR基因甲基化发生率较高。此外,肿瘤的临床分期(OR = 0.2 3,95%CI 0.0 7,0.70,P< 0.0 5)和肿瘤大小(OR = 0.19,95%CI 0.11,0.32,P< 0.0 1)也与TsHR基因甲基化有关。敏感性分析的结果表明,纳入Meta分析的研究的综合结果相当稳定。结论 基因甲基化率较高,可能与PTC的发病机制有关,可作为PTC诊断的候选标志物。另外,PTC患者TSHR基因甲基化的发生与年龄、淋巴结转移、临床分期、肿瘤大小密切相关,提示TSHR基因甲基化可作为判断PTC严重程度的指标。
PurposeTo 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.MethodsWe 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.ResultsTotally 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).ConclusionsThe 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.