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

WU Dan; DONG Ying; ZHANG Mao

Abstract：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.