临床肿瘤学杂志

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RUNX3基因启动子区甲基化与肝癌临床病理特征的Meta分析

吴丹,董莹,张矛
  

  1. 吉林省肿瘤医院放疗三科
  • 收稿日期:2014-05-30 修回日期:2014-06-19 出版日期:2014-08-31 发布日期:2014-08-31
  • 通讯作者: 张矛

A meta-analysis of association between RUNX3 gene promoter methylation and clinicopathological features of hepatocellular carcinoma

WU Dan, DONG Ying, ZHANG Mao   

  1. Third Department of Radiotherapy, Tumor Hospital of Jilin
  • Received:2014-05-30 Revised:2014-06-19 Online:2014-08-31 Published:2014-08-31
  • Contact: ZHANG Mao

摘要: 目的 探讨Runt相关转录因子3(RUNX3)基因启动子区甲基化与肝细胞癌(HCC)临床病理特征间的关系。方法 参照Cochrane协作网制定的检索策略,计算机检索MEDLINE、Cochrane Library Database、EMBASE、CINAHL、Web of Science、中国生物医学文献数据库(CBM)、万方及中国知网数据库,检索时间截止于2013年1月。收集关于RUNX3基因启动子区甲基化与HCC临床病理特征关系的研究,由2名评价者按照纳入和排除标准独立选择文献、提取资料、评价质量。采用STATA 12.0软件进行Meta分析,计算比值比(OR)及其95%可信区间(CI)并行敏感性分析和发表偏倚评估。结果 最终纳入8篇文献共包括598例研究对象,共提取513个癌组织、429个癌旁组织及85个正常肝组织。纳入结果在肿瘤组织vs.癌旁组织、肿瘤组织vs.正常组织、癌旁组织vs.正常组织、TNM分期、组织学分级和侵袭级别的比较模型中均无异质性。各模型Meta分析结果显示,癌组织RUNX3启动子区甲基化率均高于癌旁或正常组织(肿瘤组织vs.癌旁组织:OR=20.81,95%CI:13.00~31.15,P<0.001;肿瘤组织vs.正常组织:OR=19.33,95%CI:13.54~27.62,P<0.001;癌旁组织vs.正常组织:OR=1.01,95%CI:0.36~2.85,P=0.981);在癌组织中,RUNX3基因启动子区甲基化率与TNM分期、组织学分级及侵袭级别均有关,Ⅲ~Ⅳ期、3~4级和T3~T4级的RUNX3启动子区甲基化率高于Ⅰ~Ⅱ期、1~2级和T1~T2级(TNM分期:OR=1.17,95%CI:1.01~1.87,P=0.048;组织学分级:OR=1.48,95%CI:1.04~1.82,P=0.025;侵袭级别:OR=1.07,95%CI:1.00~1.72,P=0.049)。结论 HCC中RUNX3基因启动子区高甲基化,且与HCC的发生发展有关。

Abstract: Objective To explore the relationship between runtrelated transcription factor 3(RUNX3) gene promoter methylation and clinicopathological features of hepatocellular carcinoma(HCC). Methods All eligible related studies published up to January 2013 were searched out from MEDLINE, Cochrane Library Database, EMBASE, CINAHL, Web of Science, Chinese Biomedical Database(CBM), Wanfang and CNKI databases according to the retrieval strategy of Cochrance network. Two reviewers independently identified the literatures according to inclusion and exclusion criteria. Metaanalysis was performed using STATA 120 software to calculate crude odds ratio(OR) with their 95% confidence interval(95%CI).
Results A total of 8 studies comprising 598 subjects(513 carcinoma tissues, 429 paracarcinoma tissues and 85 normal liver tissues) were finally included. The included studies showed good homogeneity in the models of carcinoma tissue vs. paracarcinoma tissue, carcinoma tissue vs. normal tissue, para-carcinoma tissue vs. normal tissue, TNM stage, histological grade and invasion level. Overall, the findings demonstrated that the frequency of RUNX3 promoter methylation in carcinoma tissues was significantly higher than those of paracarcinoma and normal tissues (carcinoma tissue vs. para-carcinoma tissue: OR=20.81, 95%CI:13.0031.15, P<0.001; carcinoma tissue vs. normal tissue: OR=19.33, 95%CI: 13.54-27.62, P<0.001; para-carcinoma tissue vs. normal tissue: OR=1.01, 95%CI:0.36-2.85, P=0.981). In carcinoma tissues, the frequency of RUNX3 promoter methylation was related with TNM stage, histological grade and invasion level. The frequencies of RUNX3 promoter methylation were higher in satge ⅢⅣ versus satge Ⅰ-Ⅱ, grade 3-4 versus grade 1-2 and grade T3-T4 versus grade T1-T2 (TNM stage: OR=1.17, 95%CI: 1.01-1.87, P=0.048; histological grade: OR=1.48, 95%CI: 1.04-1.82, P=0.025; invasion level: OR=1.07, 95%CI: 1.00-1.72, P=0.049). Conclusion The RUNX3 gene promoter is hypermethylated in HCC, which indicating its relationship with the occurrence and progress of HCC.

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