抑癌DNA甲基化在乳腺癌早期筛查和辅助诊断中的价值比较:间接比较Meta分析

Comparison of DNA hypermethylation of tumor suppressor genes as diagnostic biomarkers in screening and auxiliary detection of breast cancer: an indirect comparison Meta-analysis

目的本研究利用间接比较Meta分析的方法评价在乳腺癌中众多甲基化的基因中价值较大的基因。方法计算机检索Cochrane Library、Pub Med、EMbase、Chinese Bio Medical Literature Database(CBM)、Web of Science、中国知网(China National Knowledge Infrastructure,CNKI)和万方数据库,收集涉及抑癌基因启动子甲基化与乳腺癌关系的Meta研究。采用间接比较Meta分析的方法评价在乳腺癌病人中甲基化的抑癌基因的诊断价值。结果最终共纳入10个甲基化基因(10个Meta研究),共计130个原始研究。在汇总的Meta分析中,甲基化的同源性磷酸酶-张力蛋白基因(phosphatase and tensin homolog,PTEN)比值比[odds ratio(OR)=66.16(24.48~178.82)]、人类相关转录因子基因(Runt-related transcription factor 3,RUNX3)[OR=28.88(15.48~54.25)]对乳腺癌的风险最大,虽然乳腺癌1号基因(breast cancer 1,BRCA1)[OR=2.11(1.88~2.35)]最小,但是在10个Meta研究中BRCA1的权重是57.1%。根据灵敏度相比之下,RUNX3基因[0.62(0.56~0.67)]最大,其次是脆性组氨酸三联体基因(fragile histidine triad protein,FHIT)[0.59(0.54~0.63)],但是RUNX3基因的特异度[0.95(0.91~0.97)]大于FHIT基因[0.65(0.61~0.69)]。综合甲基化基因的灵敏度和特异度,利用间接比较的方法,RUNX3基因对乳腺癌的诊断价值最大。结论在乳腺癌的早期筛查和辅助检查中,提倡对RUNX3和BRCA1甲基化的基因加以利用。

Objective To assess the comparative efficacy of diagnostic accuracy of DNA methylation biomarkers for the screening and detection of breast cancer, we conducted an indirect comparison Meta-analysis of published reports.Methods Databases including the Cochrane Library, PubMed, EMbase, Chinese BioMedical Literature Database （CBM）, Web of Science, China National Knowledge Infrastructure （CNKI） and WanFang Data were searched to collect the diagnostic trials on the Meta-analysis of aberrant DNA hypermethylation for breast cancer published until October 2016.The indirect comparison Meta-analysis was used to evaluate the diagnostic value of the included genes, and the Meta-analysis was conducted via Review manager 5.3 software.Results Ten Meta-analysis of 130 original studies were included.In summary of Meta-analysis, compared with others gene, methylation of phosphatase and tensin homolog gene （PTEN） [iodds ratio （OR）=66.16 （24.48-178.82）], methylation of Runt-related transcription factor 3 gene （RUNX3） [OR=28.88 （15.48-54.25）] had greater risk in breast cancer.Although breast cancer 1 gene （BRCA1） [OR=2.11 （1.88-2.35）] was the smallest risk for breast cancer, the weight of BRCA1 gene was up to 57.1% in all the Meta.According to the sensitivity, compared with others gene, RUNX3 [0.62 （0.56-0.67）] was the largest, followed by fragile histidine triad protein gene （FHIT） [0.59 （0.54-0.63）], but the specificity of RUNX3 [0.95 （0.91-0.97）] was greater than FHIT [0.65 （0.61-0.69）].Comprehensive sensitivity and specificity of ten genes, the largest value of RUNX3 in the diagnosis of breast cancer was found.Conclusion We advocate that RUNX3 and BRCA1 gene methylation can be used in the screening and auxiliary detection of breast cancer.