RUNX3基因启动子区甲基化与肝癌临床病理特征的Meta分析

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 Sci-ence、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。%Objective To explore the relationship between runt-related transcription factor 3( RUNX3) gene promoter methy-lation and clinicopathological features of hepatocellular carcinoma( HCC) . Methods All eligible related studies published up to Janu-ary 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 calcu-late 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 pro-moter 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 satgeⅢ-Ⅳversus satgeⅠ-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;inva-sion 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.