Emerging evidence indicates that Retinoic acid receptor-β (RARβ) is a tumor suppressor in many types of tumor. However, whether or not RARβ is a risk factor and is correlated to clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains unclear. In this report, we performed a meta-analysis to determine the effects of RARβ hypermethylation on the incidence of NSCLC and clinicopathological characteristics in human NSCLC patients. Final valuation and analysis of 1780 cancer patients from 16 eligible studies was performed. RARβ hypermethylation was found to be significantly higher in NSCLC than in normal lung tissue, the pooled OR from 7 studies including 646 NSCLC and 580 normal lung tissues, OR = 6.05, 95% CI = 3.56-10.25, p<0.00001. RARβ hypermethylation was significantly higher in adenocarcinoma (AC) compared to squamous cell carcinoma (SCC), pooled OR is 0.68 (95% CI = 0.52-0.89, p = 0.005). RARβ hypermethylation was also found to occur significantly higher in smoker (n = 232) than non-smoker (n = 213) (OR = 2.46, 95% CI = 1.54-3.93, p = 0.0002). Our results indicate that RARβ hypermethylation correlates well with an increased risk in NSCLC patients. RARβ geneinactivation caused by RARβ methylation contributes the NSCLC tumorigenesis and may serve as a potential risk factor, diagnostic marker and drug target of NSCLC.
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.
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