Niu Heng, Yang Jingyu, Yang Kunxian, Huang Yingze
aChest Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan bLandscape Laboratory, Guilin, Guangxi, China.
Medicine (Baltimore). 2017 Nov;96(46):e8630. doi: 10.1097/MD.0000000000008630.
DNA promoter methylation can suppresses gene expression and shows an important role in the biological functions of Ras association domain family 1A (RASSF1A). Many studies have performed to elucidate the role of RASSF1A promoter methylation in thyroid carcinoma, while the results were conflicting and heterogeneous. Here, we analyzed the data of databases to determine the relationship between RASSF1A promoter methylation and thyroid carcinoma.
We used the data from 14 cancer-normal studies and Gene Expression Omnibus (GEO) database to analyze RASSF1A promoter methylation in thyroid carcinoma susceptibility. The data from the Cancer Genome Atlas project (TCGA) database was used to analyze the relationship between RASSF1A promoter methylation and thyroid carcinoma susceptibility, clinical characteristics, prognosis. Odds ratios were estimated for thyroid carcinoma susceptibility and hazard ratios were estimated for thyroid carcinoma prognosis. The heterogeneity between studies of meta-analysis was explored using H, I values, and meta-regression. We adopted quality criteria to classify the studies of meta-analysis. Subgroup analyses were done for thyroid carcinoma susceptibility according to ethnicity, methods, and primers.
Result of meta-analysis indicated that RASSF1A promoter methylation is associated with higher susceptibility to thyroid carcinoma with small heterogeneity. Similarly, the result from GEO database also showed that a significant association between RASSF1A gene promoter methylation and thyroid carcinoma susceptibility. For the results of TCGA database, we found that RASSF1A promoter methylation is associated with susceptibility and poor disease-free survival (DFS) of thyroid carcinoma. In addition, we also found a close association between RASSF1A promoter methylation and patient tumor stage and age, but not in patients of different genders.
The methylation status of RASSF1A promoter is strongly associated with thyroid carcinoma susceptibility and DFS. The RASSF1A promoter methylation test can be applied in the clinical diagnosis of thyroid carcinoma.
DNA启动子甲基化可抑制基因表达，并在Ras关联结构域家族1A（RASSF1A）的生物学功能中发挥重要作用。许多研究已开展以阐明RASSF1A启动子甲基化在甲状腺癌中的作用，但其结果相互矛盾且存在异质性。在此，我们分析了数据库数据以确定RASSF1A启动子甲基化与甲状腺癌之间的关系。
我们使用来自14项癌组织与正常组织研究的数据以及基因表达综合数据库（GEO）来分析RASSF1A启动子甲基化与甲状腺癌易感性的关系。癌症基因组图谱计划（TCGA）数据库的数据用于分析RASSF1A启动子甲基化与甲状腺癌易感性、临床特征及预后之间的关系。计算甲状腺癌易感性的比值比以及甲状腺癌预后的风险比。使用H、I值及Meta回归分析Meta分析中各研究间的异质性。我们采用质量标准对Meta分析的研究进行分类。根据种族、方法及引物对甲状腺癌易感性进行亚组分析。
Meta分析结果表明，RASSF1A启动子甲基化与甲状腺癌易感性增加相关，异质性较小。同样，GEO数据库的结果也显示RASSF1A基因启动子甲基化与甲状腺癌易感性之间存在显著关联。对于TCGA数据库的结果，我们发现RASSF1A启动子甲基化与甲状腺癌易感性及无病生存期（DFS）较差相关。此外，我们还发现RASSF1A启动子甲基化与患者肿瘤分期及年龄密切相关，但在不同性别的患者中无此关联。
RASSF1A启动子的甲基化状态与甲状腺癌易感性及DFS密切相关。RASSF1A启动子甲基化检测可应用于甲状腺癌的临床诊断。
