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. 2016 Aug 26:9:5339-47.
doi: 10.2147/OTT.S77828. eCollection 2016.

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 Wu  4
Affiliations

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

Xiao-Yun Song et al. Onco Targets Ther. .

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 biomarker for the diagnosis of BC. Further large-scale studies will provide more insight into the role of RUNX3 hypermethylation in the carcinogenesis and clinical diagnosis of BC patients.

Keywords: RUNX3; breast cancer; estrogen receptor; meta-analysis; methylation; odds ratio.

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Figures

Figure 1
Figure 1
Schematic flow diagram for selection of included studies.
Figure 2
Figure 2
Comparison of RUNX3 hypermethylation in DCIS, IDC tissue and normal breast tissue. Notes: (A) Forest plot for RUNX3 methylation in DCIS and normal breast tissue. (B) Forest plot for RUNX3 methylation in IDC and normal breast tissue. Abbreviations: DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; CI, confidence interval; M–H, Mantel–Haenszel; df, degrees of freedom.
Figure 3
Figure 3
Comparison of RUNX3 hypermethylation in IDC vs benign tumor and IDC vs DCIS. Notes: (A) Forest plot for RUNX3 methylation in IDC and benign tumor. (B) Forest plot for RUNX3 methylation in IDC and DCIS. Abbreviations: DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; CI, confidence interval; M–H, Mantel–Haenszel; df, degrees of freedom.
Figure 4
Figure 4
Forest plot for RUNX3 methylation in ER positive and negative of BC. Abbreviations: BC, breast cancer; CI, confidence interval; M–H, Mantel–Haenszel; df, degrees of freedom; ER, estrogen receptor.
Figure 5
Figure 5
Funnel plot for publication bias. Notes: (A) RUNX3 methylation in DCIS and normal breast tissue; (B) RUNX3 methylation in IDC and normal breast tissue; (C) RUNX3 methylation in IDC and benign tumor; (D) RUNX3 methylation in IDC and DCIS; (E) RUNX3 methylation in ER (+) and ER (−) breast cancer. Abbreviations: DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; SE, standard error; OR, odds ratio; ER, estrogen receptor.
Figure 6
Figure 6
The clinical relevance of RUNX3 was determined in a patient survival analysis using an online database containing the expression of 22,277 genes and 20-year survival information of 3,455 breast cancer (BC) patients. Notes: (A) High RUNX3 mRNA expression was found to be correlated with better overall survival for all BC patients followed for 20 years, hazard ratio (HR) 0.78, P=0.037. (B) High RUNX3 mRNA expression was also found to be correlated with better relapse-free survival for all BC patients followed for 20 years, HR 0.8, P=0.00013.
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