Abstract
Runt-related transcription factor 3 (RUNX3) methylation plays an important role in the carcinogenesis of breast cancer (BC). However, the association between RUNX3 hypermethylation and significance of BC remains under investigation. The purpose of this study is to perform a meta-analysis and literature review to evaluate the clinicopathological significance of RUNX3 hypermethylation in BC. A comprehensive literature search was performed in Medline, Web of Science, EMBASE, Cochrane Library Database, CNKI and Google scholar. A total of 10 studies and 747 patients were included for the meta-analysis. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were evaluated and summarized respectively. RUNX3 hypermethylation was significantly correlated with the risk of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC), OR was 50.37, p < 0.00001 and 22.66, p < 0.00001 respectively. Interestingly, the frequency of RUNX3 hypermethylation increased in estrogen receptor (ER) positive BC, OR was 12.12, p = 0.005. High RUNX3 mRNA expression was strongly associated with better relapse-free survival (RFS) in BC patients. In summary, RUNX3 methylation could be a promising early biomarker for the diagnosis of BC. High RUNX3 mRNA expression is correlated to better RFS in BC patients. RUNX3 could be a potential therapeutic target for the development of personalized therapy.
Highlights
Breast cancer (BC) is the most frequently diagnosed cancer and the leading cancer related death for women worldwide, with 232,340 new cases every year [1]
The frequency of RUNX3 methylation was significantly higher in ductal carcinoma in situ (DCIS) than in normal breast tissues and the pooled odds ratios (ORs) was 50.37 with 95% confidence intervals (CIs) 12.32-205.90, z = 5.46, p < 0.00001, I2 = 0%, p = 0.76 (Figure 2)
RUNX3 methylation was significantly increased in invasive ductal carcinoma (IDC) than in benign tumor, OR was 55.65 with 95% CI 9.99-310.15, z = 4.59, p < 0.00001, I2 = 0%, p = 0.73 (Figure 4)
Summary
Breast cancer (BC) is the most frequently diagnosed cancer and the leading cancer related death for women worldwide, with 232,340 new cases every year [1]. Carcinogenesis in breast is a linear multi-step process which starts as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), advances to ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). The studies of molecular mechanism have demonstrated that the carcinogenesis involves the accumulation of various genetic alterations including loss of tumor suppressor genes and amplification of oncogenes [3]. RUNX3 plays an important role in gastric epithelial growth [5], development of dorsal root ganglia [6,7] and T-cell differentiation [8], and has a principle role in the regulation of cell proliferation, cell death, angiogenesis, as well as invasion [9,10]. RUNX3 protein regulates the growth-suppressive effects www.impactjournals.com/oncotarget
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