The clinicopathological significance of RUNX3 hypermethylation and mRNA expression in human breast cancer, a meta-analysis

Xiao-yun Song,1,* Bo-yan Li,2,* En-xiang Zhou,3 Feng-xia Wu4 1Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Breast Surgery, Inner Mongolia Forestry General Hospital, Inner Mongolia, People’s Republic of China; 3Department of General Surgery, the Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Breast Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Aberrant promoter methylation of RUNX3 has been reported in several tumors including human breast cancer (BC). However, the association between RUNX3 hypermethylation and incidence of BC remains elusive. In this study, a detailed literature search was performed in Medline and Google Scholar for related research publications. Analysis of pooled data were executed. Odds ratios with corresponding confidence intervals were determined and summarized, respectively. Finally, 13 studies were identified for the meta-analysis. Analysis of the pooled data showed that RUNX3 hypermethylation was significantly higher in both ductal carcinoma in situ and invasive ductal carcinoma (IDC) than in normal breast tissues. In addition, RUNX3 methylation was significantly higher in IDC than in benign tumor. However, RUNX3 methylation was not significantly higher in IDC than in ductal carcinoma in situ. We also determined that RUNX3 hypermethylation was significantly higher in ER positive BC than in ER negative BC. In addition, high RUNX3 mRNA expression was found to be correlated with better overall survival and relapse-free survival for all BC patients. Our results strongly support that RUNX3 hypermethylation may play an important role in BC incidence. RUNX3 methylation is a valuable early biomark