SHOX2基因启动子甲基化与肺癌关系的Meta分析

A Meta-analysis of Association between SHOX2 Gene Promoter Methylation and Lung Cancer

目的通过Meta分析的方法探讨SHOX2基因启动子甲基化与肺癌的关系。方法全面检索中国知网、万方医学数据库、维普中文期刊、Pubmed、Web of science等数据库,查找有关SHOX2基因启动子甲基化与肺癌关系的临床研究文献。搜索期限为2018年12月31日之前。应用Stata14.0软件对所得数据进行Meta分析。结果研究共纳入14篇文献,其中实验组肺癌标本1671例,对照组标本1659例,纳入最后统计数据,Meta分析结果表明,肺癌患者肿瘤组织中SHOX2基因甲基化出现的阳性风险明显高于对照组,用患者正常的肺组织标本为参照,其OR值合并效应量为18.54(95%CI:11.20~30.69,P<0.05),即肿瘤组织出现阳性的风险是对照组的18.54倍。按样本种类进行亚组分析,组织样本中OR值为33.94(95%CI:13.42~85.85,P<0.05);血浆样本中OR值为11.37(95%CI:4.33~29.84,P<0.05),灌洗液样本中OR值为24.58(95%CI:12.77~47.32,P<0.05);胸腔积液样本中OR值为5.52(95%CI:3.92~7.78,P<0.05);将纳入文献的肺恶性肿瘤的病理学类型进行亚组分析结果显示,腺癌所占比例(腺癌/腺癌+鳞癌+其他类型)小于25%以下OR值为12.33(95%CI:6.68~22.76,P<0.05),腺癌所占比例大于25%以上OR值为38.07(95%CI:17.98~80.60,P<0.05);将纳入文献的肺恶性肿瘤临床分期进行亚组分析结果表明,Ⅲ和Ⅳ期所占比例小于65%以下OR值为21.65(95%CI:11.80~39.73,P<0.05),Ⅲ和Ⅳ期所占比例大于65%以上OR值为20.34(95%CI:3.39~121.91,P<0.05)。结论肺癌患者肺癌组织中SHOX2基因启动子甲基化增高,此基因启动子甲基化和肺癌的发生可能存在相关性;SHOX2基因启动子甲基化和肺腺癌存在相关性,但与患者的临床分期无明显相关性。

Objective To evaluate the relationship between SHOX2 gene promoter methylation and lung cancer risk by meta-analysis.Methods A comprehensive search of CNKI,Wanfang Medical Database,VIP,Pubmed,Web of Science and other databases to find a clinical research literature on the relationship between SHOX2 gene promoter methylation and lung cancer.The search period is before December 31,2018.Meta-analysis of the data was performed using Stata 14.0 software.Results A total of 14 articles were included in the study.Among them,1671 cases of lung cancer specimens in the experimental group and 1659 specimens in the control group were included in the final statistical data.The results of meta-analysis showed that the positive risk of SHOX2 gene methylation in tumor tissues of lung cancer patients was significantly higher than that of the control group.The patient's normal lung tissue specimens were used as reference.The combined effect of the OR value was 18.54(95%CI:11.20 to 30.69,P<0.05),the risk of tumor tissue positive was 18.54 times that of the control group.Subgroup analysis was performed according to the sample type.The OR value of the tissue samples was 33.94(95%CI:13.42 to 88.55,P<0.05).The OR value of plasma samples was 11.37(95%CI:4.33 to 29.84,P<0.05).The OR value of the lavage fluid sample was 24.58(95%CI:12.77 to 47.32,P<0.05);the OR value of the pleural effusion sample was 5.52(95%CI:3.92 to 7.78,P<0.05).Subgroup analysis of pathological types of lung malignant tumors showed that the proportion of adenocarcinoma adenocarcinoma/adenocarcinoma+squamous cell carcinoma+other types)was less than 25%and the OR value was 12.33(95%CI:6.68 to 2.76,P<0.05),the proportion of adenocarcinoma was more than 25%and the OR value was 38.07(95%CI:17.98 to 80.60,P<0.05).The clinical stage of lung malignant tumors included in the literature was analyzed by subgroup.The results showed that:The proportion of the period and the fourth period(Ⅲphases+Ⅳphases/Ⅰphase+Ⅱphases+Ⅲphases+Ⅳphases)less than 65%below the OR value of 21.65(95%CI:11.80 to 39.73,P<0.05),Ⅲphases The ratio of theⅣphase to the fourth phase was greater than 65%and the OR value was 20.34(95%CI:3.39 to 121.91,P<0.05).Conclusion The methylation of SHOX2 gene promoter is increased in lung cancer tissue,which may be related to the occurrence of lung cancer;the methylation of SHOX2 gene promoter is related to lung adenocarcinoma,but not to the clinical stage.