Nikolaidis Christos, Nena Evangelia, Panagopoulou Maria, Balgkouranidou Ioanna, Karaglani Makrina, Chatzaki Ekaterini, Agorastos Theodoros, Constantinidis Theodoros C
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece.
Cancer Epidemiol. 2015 Oct;39(5):682-6. doi: 10.1016/j.canep.2015.07.008. Epub 2015 Jul 30.
Several studies have implicated PAX1 epigenetic regulation in cervical neoplasia. The aim of this meta-analysis was to assess PAX1 gene methylation as a potential biomarker in cervical cancer screening.
A systematical search of all major databases was performed, in order to include all relevant publications in English until December 31(st) 2014. Studies with insufficient data, conducted in experimental models or associated with other comorbidities were excluded from the meta-analysis. Summary receiver operating characteristics (SROC) for Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2(+)) versus normal, and CIN grade 3 or worse (CIN3(+)) versus normal, were estimated using the bivariate model.
Out of the 20 initially included studies, finally 7 (comprising of 1385 subjects with various stages of CIN and normal cervical pathology) met the inclusion criteria. The sensitivity of CIN2(+) versus normal was estimated to be 0.66 (CI 95%, 0.46-0.81) and the specificity 0.92 (CI 95%, 0.88-0.95). On the other hand, the sensitivity of CIN3(+) versus normal was 0.77 (CI 95%, 0.58-0.89) and the specificity 0.92 (CI 95%, 0.88-0.94). Moreover, the area under the curve (AUC) in the former case was 0.923, and in the latter 0.931.
The results of this meta-analysis support the utility of PAX1 methylation as an auxiliary biomarker in cervical cancer screening. PAX1 could be used effectively to increase the specificity of HPV DNA by detecting women with more advanced cervical abnormalities.
多项研究表明PAX1基因的表观遗传调控与宫颈肿瘤形成有关。本荟萃分析的目的是评估PAX1基因甲基化作为宫颈癌筛查潜在生物标志物的作用。
对所有主要数据库进行系统检索,以纳入截至2014年12月31日的所有英文相关出版物。数据不足、在实验模型中进行或与其他合并症相关的研究被排除在荟萃分析之外。使用双变量模型估计2级或更高级别宫颈上皮内瘤变(CIN2(+))与正常组织、以及3级或更高级别CIN(CIN3(+))与正常组织的汇总受试者工作特征(SROC)。
最初纳入的20项研究中,最终有7项(包括1385名患有不同阶段CIN和正常宫颈病理的受试者)符合纳入标准。CIN2(+)与正常组织相比的敏感性估计为0.66(95%CI,0.46 - 0.81),特异性为0.92(95%CI,0.88 - 0.95)。另一方面,CIN3(+)与正常组织相比的敏感性为0.77(95%CI,0.58 - 0.89),特异性为0.92(95%CI,0.88 - 0.94)。此外,前一种情况的曲线下面积(AUC)为0.923,后一种情况为0.931。
本荟萃分析结果支持PAX1甲基化作为宫颈癌筛查辅助生物标志物的效用。通过检测患有更晚期宫颈异常的女性,PAX1可有效提高HPV DNA检测的特异性。