定量检测SLIT2基因甲基化对高级别宫颈癌前病变的诊断价值

Diagnostic value of quantitative detection of SLIT2 methylation for cervical high grade precancerous lesion

目的探讨神经导向因子2(SLIT2)基因甲基化定量检测对于高级别宫颈癌前病变的临床诊断价值。方法收集178例高危型人乳头瘤病毒(HPV)感染患者的宫颈脱落细胞,以组织病理学诊断作为金标准,分为正常宫颈组(n=45)、低级别病变组(n=50)和高级别病变组(n=83)。采用焦磷酸测序法定量检测各样本中SLIT2基因的甲基化水平。采用受试者工作特征(ROC)曲线确定SLIT2基因的甲基化水平对高级别宫颈癌前病变的诊断阈值。结果正常宫颈组SLIT2基因的甲基化水平为(4.53±1.37)%,低级别病变组为(5.81±2.26)%,高级别病变组为(11.80±8.47)%,组间差异有统计学意义(F=27.61,P<0.001);高级别病变组高于正常宫颈组和低级别病变组(均P<0.001),正常宫颈组和低级别病变组之间差异无统计学意义(P=0.297)。SLIT2基因甲基化定量检测诊断高级别宫颈癌前病变的灵敏度为80.7%,特异度为83.2%,最佳界值为6.41%。结论采用焦磷酸测序法定量检测宫颈脱落细胞中SLIT2基因甲基化水平能够有效诊断高级别宫颈癌前病变。

Objective To explore the clinical diagnostic value of quantitative detection of the slit homologue 2 (SLIT2) methylation for cervical high grade precancerous lesions. Methods According to histopathologic diagnostic results, 178patients infected with high-risk HPV were divided into normal cervix group (n=45), low-grade lesion group (n=50) and highgradelesion group (n=83). The cervical exfoliated cells were collected in three groups. The methylation levels of SLIT2 were measured by pyrosequencing in three groups. The diagnostic threshold of SLIT2 in high grade precancerous lesions wasestimated by receiver operating characteristic (ROC) curve. Results The percentages of SLIT2 methylation were (4.53±1.37)%, (5.81±2.26)% and (11.80±8.47)% in normal cervix group, low-grade lesion group and high-grade lesion group,respectively. And the differences between three groups were statistically significant (F=27.61, P<0.001). The percentage ofSLIT2 methylation was significantly higher in high-grade lesion group than that of normal cervix group and low-grade lesiongroup (P<0.001). There was no significant difference in the percentage of SLIT2 methylation between normal cervix groupand low-grade lesion group (P=0.297). The area under the ROC curve was 0.895 and optimal cut-off value was 6.41%. The sensitivity and specificity were 80.7% and 83.2%, respectively for the detection by SLIT2 methylation. Conclusion The quantitative detection of SLIT2 gene methylation level in cervical exfoliated cells by pyrosequencing can effectively diagnose cervical high grade precancerous lesions.