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锌指蛋白582甲基化作为预测宫颈上皮内瘤变III级及以上病变的潜在生物标志物:中国人群相关研究的荟萃分析

ZNF582 methylation as a potential biomarker to predict cervical intraepithelial neoplasia type III/worse: A meta-analysis of related studies in Chinese population.

作者信息

Li Na, He Ya, Mi Peng, Hu Yuanjing

机构信息

Department of Gynecologic Oncology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Hospital.

Graduate School.

出版信息

Medicine (Baltimore). 2019 Feb;98(6):e14297. doi: 10.1097/MD.0000000000014297.

Abstract

OBJECTIVE

DNA methylation markers have been assessed as potential biomarkers for early cervical cancer detection. Herein, we evaluated the diagnostic performance of zinc finger protein 582 (ZNF582) methylation for cervical cancer detection.

METHODS

Eligible studies were systematically searched from the electronic databases. The quality of enrolled studies was evaluated using the second version of the check list for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve using Stata 14.0 software. Cochran's Q test and I statistics were applied to assess heterogeneity among studies. Publication bias was evaluated by the Deeks' funnel plot asymmetry test.

RESULTS

Seven studies composed of 1749 patients were eventually included. The pooled sensitivity of ZNF582 methylation was estimated to be 0.71 [95% confidence interval (CI): 0.67-0.75] in differentiating patients with cervical intraepithelial neoplasia type III/worse (CIN3+), corresponding to a specificity of 0.81 (95% CI: 0.79-0.83) and area under the curve (AUC) of 0.85. Our stratified analysis suggested that sequential combined of HPV DNA and ZNF582 methylation test (AUC, sensitivity, and specificity of 0.876, 0.75, and 0.87, respectively) achieved higher diagnostic accuracy than single HPV DNA testing test (AUC, sensitivity and specificity of 0.669, 0.96, and 0.41, respectively).

CONCLUSIONS

ZNF582 methylation has a prospect to be an auxiliary biomarker for cervical cancer screening. A new strategy of co-testing HPV DNA and ZNF582 methylation test in cervical scrapings confers an improved diagnostic accuracy than single HPV DNA testing.

摘要

目的

DNA甲基化标记物已被评估为早期宫颈癌检测的潜在生物标志物。在此,我们评估了锌指蛋白582(ZNF582)甲基化在宫颈癌检测中的诊断性能。

方法

从电子数据库中系统检索符合条件的研究。使用诊断准确性研究质量评估清单(QUADAS - 2)的第二版评估纳入研究的质量。采用双变量Meta分析模型,使用Stata 14.0软件绘制汇总接受者操作特征(SROC)曲线。应用Cochran's Q检验和I统计量评估研究间的异质性。通过Deeks漏斗图不对称性检验评估发表偏倚。

结果

最终纳入7项研究,共1749例患者。ZNF582甲基化在鉴别宫颈上皮内瘤变III级及以上(CIN3 +)患者中的合并敏感性估计为0.71 [95%置信区间(CI):0.67 - 0.75],相应的特异性为0.81(95% CI:0.79 - 0.83),曲线下面积(AUC)为0.85。我们的分层分析表明,HPV DNA与ZNF582甲基化检测序贯联合(AUC、敏感性和特异性分别为0.876、0.75和0.87)比单一HPV DNA检测(AUC、敏感性和特异性分别为0.669、0.96和0.41)具有更高的诊断准确性。

结论

ZNF582甲基化有望成为宫颈癌筛查的辅助生物标志物。宫颈刮片中HPV DNA与ZNF582甲基化联合检测的新策略比单一HPV DNA检测具有更高的诊断准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d68/6380660/41a6b4f87c0d/medi-98-e14297-g001.jpg

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