Ding Zhenyu, Jiang Tong, Piao Ying, Han Tao, Han Yaling, Xie Xiaodong
Department of Oncology, General Hospital of Shenyang Military Region, Shenyang City, Liaoning Province, People's Republic of China.
Laboratory of Military Health in Cold Region, Center for Disease Control and Prevention of Shenyang Military Region, Shenyang City, Liaoning Province, People's Republic of China.
Onco Targets Ther. 2015 Jan 19;8:211-22. doi: 10.2147/OTT.S75827. eCollection 2015.
Previous studies investigating the association between adenomatous polyposis coli (APC) gene promoter methylation and colorectal cancer (CRC) have yielded conflicting results. The aim of this study was to comprehensively evaluate the potential application of the detection of APC promoter methylation to the prevention and treatment of CRC. PubMed, Embase, and MEDLINE (results updated to October 2014) were searched for relevant studies. The effect size was defined as the weighted odds ratio (OR), which was calculated using either the fixed-effects or random-effects model. Prespecified subgroup and sensitivity analyses were conducted to evaluate potential heterogeneity among the included studies. Nineteen studies comprising 2,426 participants were selected for our meta-analysis. The pooled results of nine studies comprising a total of 740 subjects indicated that APC promoter methylation was significantly associated with CRC risk (pooled OR 5.53; 95% confidence interval [CI] 3.50-8.76; P<0.01). Eleven studies with a total of 1,219 patients evaluated the association between APC promoter methylation and the presence of CRC metastasis, and the pooled OR was 0.80 (95% CI 0.44-1.46; P=0.47). A meta-analysis conducted with four studies with a total of 467 patients found no significant correlation between APC promoter methylation and the presence of colorectal adenoma (pooled OR 1.85; 95% CI 0.67-5.10; P=0.23). No significant correlation between APC promoter methylation and patients' Dukes' stage, TNM stage, differentiation grade, age, or sex was identified. In conclusion, APC promoter methylation was found to be significantly associated with a higher risk of developing CRC. The findings indicate that APC promoter methylation may be a potential biomarker for the carcinogenesis of CRC.
既往研究探讨腺瘤性息肉病 coli（APC）基因启动子甲基化与结直肠癌（CRC）之间的关联，结果相互矛盾。本研究旨在全面评估检测 APC 启动子甲基化在 CRC 防治中的潜在应用价值。检索了 PubMed、Embase 和 MEDLINE（检索结果更新至 2014 年 10 月）以查找相关研究。效应量定义为加权比值比（OR），使用固定效应模型或随机效应模型进行计算。进行预设的亚组分析和敏感性分析以评估纳入研究之间的潜在异质性。我们的荟萃分析纳入了 19 项研究，共 2426 名参与者。9 项研究（共 740 名受试者）的汇总结果表明，APC 启动子甲基化与 CRC 风险显著相关（汇总 OR 为 5.53；95%置信区间[CI]为 3.50 - 8.76；P<0.01）。11 项研究（共 1219 名患者）评估了 APC 启动子甲基化与 CRC 转移存在之间的关联，汇总 OR 为 0.80（95%CI 为 0.44 - 1.46；P = 0.47）。对 4 项研究（共 467 名患者）进行的荟萃分析发现，APC 启动子甲基化与结直肠腺瘤的存在之间无显著相关性（汇总 OR 为 1.85；95%CI 为 0.67 - 5.10；P = 0.23）。未发现 APC 启动子甲基化与患者的 Dukes 分期、TNM 分期、分化程度、年龄或性别之间存在显著相关性。总之，发现 APC 启动子甲基化与发生 CRC 的较高风险显著相关。研究结果表明，APC 启动子甲基化可能是 CRC 致癌作用的潜在生物标志物。
