SDC2基因甲基化对结直肠癌诊断价值的Meta分析

The diagnosis value of SDC2 methylation for colorectal cancer:a Meta-analysis

目的通过Meta分析方法评价多配体蛋白聚糖2(Syndecan-2,SDC2)基因甲基化作为生物标志物诊断结直肠癌(colorectal cancer,CRC)的价值。方法计算机检索PubMed、Cochrane Library、Embase、Web of Science、CBM、万方、知网、维普数据库,查找建库至2020年9月1日有关SDC2基因甲基化与CRC的研究,按照纳入及排除标准严格筛选文献,提取信息并依据QUADAS-2准则对文献进行质量评价。检验阈值效应及非阈值效应,计算合并灵敏度(sensitivity,Sen)、特异度(specificity,Spe)、阳性似然比(positive likelihood ratio,PLR)、阴性似然比(negative likelihood ratio,NLR)、诊断比值比(diagnostic odds ratio,DOR),绘制综合受试者工作特征曲线(summary receiver operating characteristic curve,SROC)并计算曲线下面积(area under curve,AUC)。采用亚组分析、敏感性分析探讨研究异质性。Deek’s漏斗图用以评价纳入文献偏倚大小。结果共纳入符合标准的文献11篇,包括1419例CRC患者和1363名健康对照者。SDC2甲基化诊断CRC的Sen_(合并)=0.77(95%CI:0.65~0.86),Spe_(合并)=0.94(95%CI:0.92~0.96),PLR_(合并)=14.17(95%CI:9.14~21.99),NLR_(合并)=0.24(95%CI:0.16~0.38),DOR_(合并)=58.28(95%CI:28.25~120.20),AUC=0.95(95%CI:0.93~0.97)。亚组分析结果显示,粪便SDC2甲基化对CRC的诊断价值(DOR_(合并)=84.23,95%CI:55.72~127.35)明显高于血液组(DOR_(合并)=33.27,95%CI:8.05~137.56)。亚洲地区SDC2甲基化对CRC的诊断价值(DOR_(合并)=76.44,95%CI:56.03~104.30)明显高于非亚洲地区(DOR_(合并)=16.50,95%CI:2.97~91.52)。Deek’s漏斗图提示,本研究不存在显著发表偏倚(P=0.840)。结论SDC2基因甲基化对CRC具有极高的诊断价值。

Objective To evaluate the value of SDC2 methylation as a biomarker in the diagnosis of colorectal cancer(CRC)by Meta-analysis.Methods PubMed,Cochrane Library,Embase,Web of Science,CBM,WanFang,CNKI and VIP databases were searched for the studies on SDC2 gene methylation in CRC by Sep.1st,2020.The literatures were screened and the data were extracted strictly according to included and excluded criterion.The quality of the studies was evaluated by the QUADAS-2 standard.The threshold effect and non-threshold effect were tested,and the pooled weighted sensitivity(Sen),specificity(Spe),positive likelihood ratio(PLR),negative likelihood ratio(NLR),and diagnostic odds ratio(DOR)were calculated.The summary receiver operating characteristic curve(SROC),area under curve(AUC),likelihood ratio point diagram and Fagan diagram were drawn.Subgroup analysis and sensitivity analysis were used to explore study heterogeneity,and Deek’s funnel plot was used to evaluate published bias.Results A total of 11 studies that met the standard were included,with a total of 1419 CRC patients and 1363 healthy normal controls.The pooled Sen,Spe,PLR,NLR,DOR and AUC of SDC2 methylation in the diagnosis of CRC were 0.77(95%CI:0.65-0.86),0.94(95%CI:0.92-0.96),14.17(95%CI:9.14-21.99),0.24(95%CI:0.16-0.38),58.28(95%CI:28.25-120.20)and 0.95(95%CI:0.93-0.97),respectively.Subgroup analysis showed that the stool SDC2 methylation had significantly higher diagnostic value(pooled DOR=84.23,95%CI:55.72-127.35)than that of blood group(pooled DOR=33.27,95%CI:8.05-137.56).The Asian group had significantly higher diagnostic value(pooled DOR=76.44,95%CI:56.03-104.30)than that in the non-Asian group(pooled DOR=16.50,95%CI:2.97-91.52).The result of the Deek’s funnel chart indicated that there was no published bias(P=0.840).Conclusion SDC2 gene methylation has excellent diagnostic value for CRC.