Zhao Tie, Afrifa Justice, Wang Dong, Yu Jingcui
Scientific Research Centre, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
Department of Medical Laboratory Science, University of Cape Coast, Cape Coast, Ghana.
EXCLI J. 2020 Apr 7;19:476-489. doi: 10.17179/excli2020-1102. eCollection 2020.
The epigenetic silencing of tumor suppressor genes by promoter methylation plays an increasingly important role in cancer research. A number of studies have reported the contribution of HIC1 promoter methylation towards the occurrence and development of solid tumors, even though HIC1 promoter methylation has also been found in normal and benign tissue samples. We sought to perform a more accurate and comprehensive meta-analysis to assess the association between HIC1 promoter methylation and cancer risk. We searched and retrieved all published studies on HIC1 promoter methylation in PubMed, Google Scholar, Embase, Cochrane Library, and Web of Science databases. After two reviewers checked the studies and extracted the necessary data independently, the meta-analysis was performed using STATA 12.0 software. A total of 14 case-control studies (949 cancer patients, 282 benign, and 371 normal controls) were included in our study. We report a significantly elevated HIC1 promoter methylation in tumor samples compared to normal ( = 7.02, 95 % 3.12-15.78, < 0.001) and benign controls ( = 2.69, 95 % 1.13-6.42, = 0.025). Subgroup analysis stratified by ethnicity showed a significantly reduced heterogeneity among North American = 0.0 %, = 0.502) and European ( = 33.7 %, = 0.183) samples. In addition, heterogeneity was significantly reduced among MSP based detection method ( = 36.4 %, = 0.139) when samples were stratified based on the methylation detection methods. The overall outcome demonstrated that HIC1 promoter methylation may be involved in the occurrence and development of solid tumors and has the potential to serve as an epigenetic maker in various specific tumors.
启动子甲基化导致的肿瘤抑制基因表观遗传沉默在癌症研究中发挥着越来越重要的作用。尽管在正常和良性组织样本中也发现了HIC1启动子甲基化,但多项研究报告了HIC1启动子甲基化对实体瘤发生发展的影响。我们试图进行更准确、全面的荟萃分析,以评估HIC1启动子甲基化与癌症风险之间的关联。我们在PubMed、谷歌学术、Embase、Cochrane图书馆和Web of Science数据库中搜索并检索了所有已发表的关于HIC1启动子甲基化的研究。在两名审稿人独立检查研究并提取必要数据后,使用STATA 12.0软件进行荟萃分析。我们的研究共纳入了14项病例对照研究(949例癌症患者、282例良性对照和371例正常对照)。我们报告,与正常对照(比值比 = 7.02,95%置信区间 3.12 - 15.78,P < 0.001)和良性对照(比值比 = 2.69,95%置信区间 1.13 - 6.42,P = 0.025)相比,肿瘤样本中HIC1启动子甲基化显著升高。按种族分层的亚组分析显示,北美样本(I² = 0.0%,P = 0.502)和欧洲样本(I² = 33.7%,P = 0.183)之间的异质性显著降低。此外,当根据甲基化检测方法对样本进行分层时,基于甲基化特异性PCR(MSP)检测方法的样本间异质性显著降低(I² = 36.4%,P = 0.139)。总体结果表明,HIC1启动子甲基化可能参与实体瘤的发生发展,并有可能作为各种特定肿瘤的表观遗传标志物。