Liu Haifeng, Meng Xia, Wang Jingyi
The 2nd Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, China.
The 2nd Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, China
Int J Gynecol Cancer. 2020 Oct;30(10):1488-1492. doi: 10.1136/ijgc-2019-001144. Epub 2020 Jul 2.
DNA methylation is currently found to be associated with the progression of cervical intraepithelial neoplasia and the development of cervical cancer. The aim of this study was to analyze the role of real time quantitative methylation detection of the PAX1 gene in cervical cancer screening.
All eligible patients who underwent multiple detections for cervical cancer were assigned to the normal cervical group (n=21), cervical intraepithelial neoplasia I group (n=7), cervical intraepithelial neoplasia II+III group (n=12), or invasive cervical cancer group (n=14) based on pathological gradings. The methylation level of the PAX1 gene was detected using the real time quantitative methylation specific polymerase chain reaction assay and assessed by △Cp value. The diagnostic performance of PAX1 methylation detection was compared with folic acid receptor mediated diagnosis, the Thinprep cytology test, and human papilloma virus (HPV) testing.
The △Cp value in the invasive cervical cancer group was (6.15±4.07), significantly lower than that in the other groups (F=26.45, p<0.001). The area under the curve (AUC) of PAX1 methylation detection was 0.902 (95% confidence interval (CI) 0.817-0.986; p<0.001), and sensitivity and specificity were 92.30% and 78.60% when the cut-off value of △Cp was 13.28. The AUC of PAX1 methylation detection was notably larger compared with 0.709 for folic acid receptor mediated diagnosis (95% CI 0.568-0.849, p=0.009), 0.702 for the Thinprep cytology test (95% CI 0.559-0.844, p=0.015), and 0.655 for HPV testing (95% CI 0.508-0.802, p=0.014).
Through quantitative methylation specific polymerase chain reaction assay characterized by rapid screening and simple operation, the methylation detection of the PAX1 gene exhibited a higher diagnostic performance and may be a promising method for cervical cancer screening.
目前发现DNA甲基化与宫颈上皮内瘤变的进展及宫颈癌的发生有关。本研究旨在分析PAX1基因实时定量甲基化检测在宫颈癌筛查中的作用。
将所有接受多次宫颈癌检测的符合条件的患者,根据病理分级分为正常宫颈组(n = 21)、宫颈上皮内瘤变I组(n = 7)、宫颈上皮内瘤变II + III组(n = 12)或浸润性宫颈癌组(n = 14)。采用实时定量甲基化特异性聚合酶链反应法检测PAX1基因的甲基化水平,并通过△Cp值进行评估。将PAX1甲基化检测的诊断性能与叶酸受体介导诊断、薄层液基细胞学检测及人乳头瘤病毒(HPV)检测进行比较。
浸润性宫颈癌组的△Cp值为(6.15±4.07),显著低于其他组(F = 26.45,p < 0.001)。PAX1甲基化检测的曲线下面积(AUC)为0.902(95%置信区间(CI)0.817 - 0.986;p < 0.001),当△Cp的截断值为13.28时,灵敏度和特异度分别为92.30%和78.60%。与叶酸受体介导诊断的AUC 0.709(95% CI 0.568 - 0.849,p = 0.009)、薄层液基细胞学检测的AUC 0.702(95% CI 0.559 - 0.844,p = 0.015)及HPV检测的AUC 0.655(95% CI 0.508 - 0.802,p = 0.014)相比,PAX1甲基化检测的AUC明显更大。
通过快速筛查、操作简单的定量甲基化特异性聚合酶链反应法,PAX1基因的甲基化检测表现出更高的诊断性能,可能是一种有前景的宫颈癌筛查方法。