Department of surgery oncology, Shandong cancer hospital, Jinan, China.
Tianjin Medical University General Hospital, Tianjin Lung Cancer Institute, Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin, China.
PLoS One. 2014 May 5;9(5):e96163. doi: 10.1371/journal.pone.0096163. eCollection 2014.
Hypermethylation of CpG islands in tumor suppressor gene plays an important role in carcinogenesis. Many studies have demonstrated that hypermethylation in promoter region of RARβ gene could be found with high prevalence in tumor tissue and autologous controls such as corresponding non-tumor lung tissue, sputum and plasma of the NSCLC patients. But with the small number subjects included in the individual studie, the statistical power is limited. Accordingly, we performed this meta-analysis to further asses the relationship of methylation prevalence between the cancer tissue and atuologous controls (corresponding non-tumor lung tissue, sputum and plasma).
The published articles about RARβ gene promoter hypermethyltion were identified using a systematic search strategy in PubMed, EMBASE and CNKI databases. The pooled odds ratio (OR) of RARβ promoter methylation in lung cancer tissue versus autologous controls were calculated.
Finally, eleven articles, including 1347 tumor tissue samples and 1137 autologous controls were included in this meta-analysis. The pooled odds ratio of RARβ promoter methylation in cancer tissue was 3.60 (95%CI: 2.46-5.27) compared to autologous controls with random-effect model. Strong and significant correlation between tumor tissue and autologous controls of RARβ gene promoter hypermethylation prevalence across studies (Correlation coefficient 0.53) was found.
RARβ promoter methylation may play an important role in carcinogenesis of the NSCLC. With significant methylation prevalence correlation between tumor tissue and autologous of this gene, methylation detection may be a potential method for searching biomarker for NSCLC.
抑癌基因 CpG 岛的高甲基化在肿瘤发生中起重要作用。许多研究表明,RARβ 基因启动子区域的高甲基化在肿瘤组织和自体对照(如相应的非肿瘤肺组织、痰液和 NSCLC 患者的血浆)中普遍存在。但由于个体研究中纳入的受试者数量较少,统计效力有限。因此,我们进行了这项荟萃分析,以进一步评估癌症组织与自体对照(相应的非肿瘤肺组织、痰液和血浆)之间甲基化流行率的关系。
使用系统搜索策略在 PubMed、EMBASE 和 CNKI 数据库中确定关于 RARβ 基因启动子高甲基化的已发表文章。计算 RARβ 启动子甲基化在肺癌组织与自体对照中的合并优势比(OR)。
最终,这项荟萃分析纳入了 11 篇文章,包括 1347 个肿瘤组织样本和 1137 个自体对照。采用随机效应模型,癌症组织中 RARβ 启动子甲基化的合并优势比为 3.60(95%CI:2.46-5.27)。研究间 RARβ 基因启动子高甲基化流行率存在强烈且显著的相关性(相关系数 0.53)。
RARβ 启动子甲基化可能在 NSCLC 的发生中起重要作用。由于该基因肿瘤组织与自体对照之间存在显著的甲基化流行率相关性,因此甲基化检测可能是寻找 NSCLC 生物标志物的一种潜在方法。