中国地区ctDNA对乳腺癌诊断价值的Meta分析
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摘要
目的系统评价国内循环肿瘤DNA诊断乳腺癌的价值。方法查找清华同方数据库、万方数据库、维普数据库、中国生物医学文献数据库、PubMed、EMBASE、Cochrane library数据库中有关国内循环肿瘤DNA诊断乳腺癌的诊断性试验,检索时限均为从建库至2017年12月21日。由2位研究者独立筛选文献、提取数据和评价纳入研究的方法学质量后,使用Meta-Disc1.4软件对纳入研究进行综合定量评价,并绘制受试者工作特征曲线(ROC曲线),对循环肿瘤DNA诊断中国人群乳腺癌的准确性进行评估,使用STATA13.0软件进行发表偏倚检验。结果共纳入7篇文献,合并灵敏度为0.85(95%CI:0.82～0.87)、特异度为0.86(95%CI:0.84～0.89)、阳性似然比为6.477(95%CI:3.496～12.000)、阴性似然比为0.173(95%CI:0.102～0.296)、合并诊断比值比为39.94(95%CI:14.07～113.37),ROC曲线下面积为0.928 5。纳入文献存在异质性,异质性来源于研究地区和目标基因。对纳入的研究作Deeks图,提示不存在明显的发表偏移。结论循环肿瘤DNA对中国人群乳腺癌诊断价值较高,在临床实践过程中可以通过联合其他项目检测以提高对乳腺癌的诊断准确性。
Objective To systematically review the diagnostic value of circulating tumor DNA for breast cancer in China.Methods CNKI,Wanfang Data,VIP,CBM,EMBASE,Cochrane library were searched from inception to December 21,2017,to collect diagnostic studies about circulating tumor DNA for breast cancer in China.Two reviewers independently screened literature,extracted data and assessed the methodological quality of included studies.Statistic analyses were performed by software Meta-Disc1.4 vision,and summary receive operating characteristic curve(ROC curve)was performed.The publication bias test was performed using STATA 13 software.Results A total of 7 studies were finally included.The pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,and diagnostic odds ratio were 0.85(95%CI:0.82-0.87),0.86(95%CI:0.84-0.89),6.477(95%CI:3.496-12.000),0.173(95%CI:0.102-0.296),respectively.The pool diagnostic odds ratio was 39.94(95%CI:14.07-113.37)and area under the ROC curve was0.928 5.There was heterogeneity in the included studies,and subgroup analysis suggested that heterogeneity was derived from the study area and target genes.The deeks suggested the publication bias was not significant.Conclusion Current evidence indicates that circulating tumor DNA has high diagnostic value for breast cancer in Chinese population,and the accuracy of breast cancer diagnosis can be improved by joining the other project detection in clinical practice.
Objective To systematically review the diagnostic value of circulating tumor DNA for breast cancer in China.Methods CNKI,Wanfang Data,VIP,CBM,EMBASE,Cochrane library were searched from inception to December 21,2017,to collect diagnostic studies about circulating tumor DNA for breast cancer in China.Two reviewers independently screened literature,extracted data and assessed the methodological quality of included studies.Statistic analyses were performed by software Meta-Disc1.4 vision,and summary receive operating characteristic curve(ROC curve)was performed.The publication bias test was performed using STATA 13 software.Results A total of 7 studies were finally included.The pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,and diagnostic odds ratio were 0.85(95%CI:0.82-0.87),0.86(95%CI:0.84-0.89),6.477(95%CI:3.496-12.000),0.173(95%CI:0.102-0.296),respectively.The pool diagnostic odds ratio was 39.94(95%CI:14.07-113.37)and area under the ROC curve was0.928 5.There was heterogeneity in the included studies,and subgroup analysis suggested that heterogeneity was derived from the study area and target genes.The deeks suggested the publication bias was not significant.Conclusion Current evidence indicates that circulating tumor DNA has high diagnostic value for breast cancer in Chinese population,and the accuracy of breast cancer diagnosis can be improved by joining the other project detection in clinical practice.
引文
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[15]WONG E M,SOUTHEY M C,FOX S B,et al.Constitutional methylation of the BRCA1promoter is specifically associated with BRCA1 mutation-associated pathology in early-onset breast cancer[J].Cancer Prevention Res,2011,4(1):23-33.
[16]李甫梧.基于DNA甲基化特异性位点区分癌症种类以及同种癌症分型并定量检测血液中的循环肿瘤细胞[D].上海:中国科学院研究生院,2016.
[2]BRAY F,FERLAY J,SOERJOMATARAM I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in 185countries[J],CA Cancer J Clin,2018,68(6):394-424.
[3]FAN L,STRASSER-WEIPPL K,LI J J,et al.Breast cancer in China[J].Lancet Oncol,2014,15(7):279-289.
[4]LEON S A,SHAPIRO B,SKLAROFF D M,et al.Free DNA in the serum of cancer patients and the effect of therapy[J].Cancer Res,1977,37(3):646-650.
[5]WANG H,LIU Z,XIE J,et al.Quantitation of cell-free DNA in blood is a potential screening and diagnostic maker of breast cancer:a Meta-analysis[J].Oncotarget,2017,60(8):102336-102345.
[6]WHITING P F,RUTJES A W,WESTWOOD M E,et al.QUADAS-2:a revised tool for the quality assessment of diagnostic accuracy studies[J].Annals Internal Med,2011,155(8):529-536.
[7]HUANG Z H,LI L H,HUA D.Quantitative analysis of plasma circulating DNA at diagnosis and during followup of breast cancer patients[J].Cancer Lett,2006,243(1):64-70.
[8]薛建祥,龚波,俞菁,等.乳腺癌患者血清游离DNA的定量检测[J].肿瘤,2011,31(12):1099-1102.
[9]GONG B,XUE J,YU J,et al.Cell-free DNA in blood is apotential diagnostic biomarker of breast cancer[J].Oncology Letters,2012,3(4):897-900.
[10]叶坤,张连生,刘冲.血浆游离DNA含量在乳腺癌诊断中的临床意义[J].今日健康,2015,20(12):433.
[11]ZHANG L,SONG X,WANG X,et al.Circulating DNAof HOTAIR in serum is a novel biomarker for breast cancer[J].Breast Cancer Res Treat,2015,152(1):199-208.
[12]顾益凤,朱自力,张金业,等.乳腺癌中血浆游离DNA含量和完整性的临床应用[J].检验医学,2017,32(8):671-676.
[13]俞菁,龚波,李海川,等.乳腺癌患者血清游离DNA与相关miRNA的表达水平[J].中国妇幼保健,2017,32(19):4651-4653.
[14]TANG S,WEI L,SUN Y,et al.CA153in breast secretions as a potential molecular marker for diagnosing breast cancer:a Meta analysis[J].PLoS One,2016,11(9):e0163030.
[15]WONG E M,SOUTHEY M C,FOX S B,et al.Constitutional methylation of the BRCA1promoter is specifically associated with BRCA1 mutation-associated pathology in early-onset breast cancer[J].Cancer Prevention Res,2011,4(1):23-33.
[16]李甫梧.基于DNA甲基化特异性位点区分癌症种类以及同种癌症分型并定量检测血液中的循环肿瘤细胞[D].上海:中国科学院研究生院,2016.