APC基因启动子甲基化与肺癌关联的Meta分析

Association between APC Promoter Methylation and Lung Cancer:A Meta-analysis

目的探讨结肠腺瘤样息肉病蛋白(adenornatous polyposis coil,APC)基因启动子甲基化与肺癌关联及其标识早期肺癌的可能性,为肺癌诊断提供依据。方法通过检索PubMed、Web of Science、Embase、中国知网、万方医学、维普等数据库,查找APC基因甲基化与肺癌相关性的研究。检索时间为建库至2020年2月7日。根据PRISMA规则,按照预先制定的纳入排除标准对文献进行筛选,并对纳入的文献进行方法学质量评价、数据提取。使用Stata15和R 3.6.1软件对所得数据进行统计学分析。结果共纳入来自10篇文献的12项病例对照研究,包括1 190例病例和606例对照。根据异质性检验结果,I2=58%,采用随机效应模型合并效应值,合并后OR值为9.84(95%CI:5.03~19.27,P<0.05),即APC基因甲基化的肺癌风险是一般人群的9.84倍。亚组分析结果显示,组织(OR=5.24,95%CI:1.06~25.92)、血液(OR=9.58,95%CI:5.98~15.35)及痰液(OR=36.59,95%CI:4.86~275.36)三种生物样本APC基因甲基化均与肺癌存在显著关联;APC基因甲基化的肺癌风险与肺腺癌比例及老年人比例相关(P<0.05),但与临床分期无显著关联(P> 0.05)。结论 APC基因启动子甲基化可能作为肺癌诊断的潜在分子标志物。

Objective To assess the association between adenornatous polyposis coil(APC)promoter methylation and lung cancer and the possibility of identifying early-stage lung cancer,and to provide the basis for the diagnosis of lung cancer.Methods Literature search for studies on association between APC promoter methylation and lung cancer published up to February 7,2020 was conducted in PubMed,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),WanFang Med Online,and VIP database.Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,studies were selected based on the prespecified inclusion and exclusion criteria,and subjected to methodological quality assessment and data extraction.Stata 15 and R 3.6.1 were used for statistical analysis.Results A total of 12 case-control studies from 10 publications were included,involving 1190 cases and 606 controls.According to heterogeneity test(I2=58%),a random effect model was used to merge the pooled effect,and the odds ratio(OR)was 9.84(95%CI:5.03-19.27,P<0.05),which indicates that the risk of lung cancer in population with APC promoter methylation was 9.84 times higher than that in general population.Subgroup analysis showed a significant association between APC promoter methylation and lung cancer in tissue(OR=5.24,95%CI:1.06-25.92),blood(OR=9.58,95%CI:5.98-15.35),and sputum(OR=36.59,95%CI:4.86-275.36).Moreover,the risk of lung cancer with APC promoter methylation was significantly related to the proportion of lung adenocarcinoma and age(P<0.05),but not to clinical stage(P>0.05).Conclusion APC promoter methylation may be a potential biomarker for lung cancer diagnosis.