宫颈上皮内瘤变和宫颈癌中LMX1A和PAX1基因甲基化的定量分析

发布时间：2018-03-25 04:31

本文选题：宫颈癌　切入点：宫颈上皮内瘤变　出处：《中国癌症杂志》2015年01期

【摘要】：背景与目的:DNA甲基化是宫颈上皮癌变过程中常见的表观遗传改变。本研究旨在检测同源盒转录因子1ɑ(LMX1A)基因和配对盒基因家族PAX1基因在浸润性宫颈鳞癌(invasive cervical cancers,ICC)组织中的甲基化水平,评估其作为分子标志物用于区分各级别宫颈病变的潜在临床价值。方法:在32例低级别宫颈上皮内瘤变(low-grade cervical intraepithelial neoplasia,LG-CIN)、34例高级别宫颈上皮内瘤变(high-grade cervical intraepithelial neoplasia,HG-CIN)、27例ICC病变宫颈组织和28例慢性宫颈炎为正常对照组(negative for intraepithelial lesion or malignancy,NLM)中,采用巢式PCR和焦硫酸测序(pyrosequencing)技术定量分析LMX1A基因的6个位点和PAX1基因的9个位点的甲基化。并通过受试者工作特征曲线下面积(receiver operating characteristic curve,ROC)的计算获得上述基因的甲基化检测用于诊断各级别宫颈病变的准确性。结果:宫颈癌中的LMX1A基因6个位点的甲基化平均水平为14.36%,明显高于HG-CIN病变的4.70%、LG-CIN病变的5.05%和NLM的4.53%(P0.01)。宫颈癌中PAX1基因9个位点的甲基化平均水平为41.97%,明显高于HG-CIN的10.21%(P0.01);而后者又明显高于LG-CIN的5.55%和NLM的4.92%(P0.01)。检测LMX1A基因甲基化和PAX1基因甲基化水平鉴别宫颈癌的ROC曲线下面积分别为0.603(P=0.104)和0.883(P0.001)。经ROC曲线下面积计算获得最佳PAX1基因甲基化水平的界定值为20.50%,其诊断浸润性宫颈癌的灵敏度为81%、特异度为93%。当PAX1基因甲基化水平界定值为9.58%时,其检测浸润性宫颈癌的灵敏度为89%、特异度为84%。结论:定量分析宫颈组织中的PAX1基因甲基化将有可能作为分子标志物用于浸润癌的鉴别诊断,而LMX1A基因的甲基化检测临床价值有限。
[Abstract]:Background & AIM: PAX1 methylation is a common epigenetic change in cervical epithelial carcinogenesis. The aim of this study was to detect homologous cassette transcription factor 1 (LMX1A) gene and pairing box gene family PAX1 gene in invasive cervical carcinomas (ICCCs) of invasive cervix cervix. Methylation level, To evaluate its potential clinical value as a molecular marker in differentiating cervical lesions of various grades. Methods: Thirty-four cases of high-grade cervical intraepithelial neoplasms with high-grade cervical intraepithelial neoplasia HG-CINA of 27 cases with ICC lesions were studied in 32 cases of low-grade cervical intraepithelial neoplasia intraepithelial neoplasia of low grade cervical intraepithelial neoplasms. Tissue and 28 cases of chronic cervicitis were included in normal control group: negative for intraepithelial lesion or malignant NLM. The methylation of 6 sites of LMX1A gene and 9 sites of PAX1 gene were quantitatively analyzed by nested PCR and pyrosulphuric acid sequencing techniques. The A of the above gene was obtained by calculating the area of receiver operating characteristic curveroc under the operating characteristic curve of the subjects. Results: the average methylation level of 6 LMX1A loci in cervical cancer was 14.36, which was significantly higher than that of 4.70% in HG-CIN and 4.53% in NLM. PAX1 gene 9 was found in cervical cancer. The average methylation level of each locus was 41.97, which was significantly higher than that of HG-CIN (10.21%), and the latter was significantly higher than that of LG-CIN (5.55%) and NLM (4.92%). The areas under ROC curve of detecting LMX1A gene methylation and PAX1 gene methylation were 0.603P0.104) and 0.883mP0.001g respectively. The optimum methylation level of PAX1 gene was calculated by ROC curve. The sensitivity and specificity of PAX1 gene methylation level were 81 and 933, respectively. When the methylation level of PAX1 gene was 9.58, the sensitivity was 81 and the specificity was 93.When the methylation level of PAX1 gene was 9.58, Its sensitivity in detecting invasive cervical carcinoma is 89 and the specificity is 84. Conclusion: quantitative analysis of PAX1 gene methylation in cervical tissue may be used as a molecular marker for differential diagnosis of invasive carcinoma. The clinical value of methylation detection of LMX1A gene is limited.
【作者单位】：复旦大学附属肿瘤医院妇瘤科复旦大学上海医学院肿瘤学系;复旦大学附属闵行医院妇产科;上海市计划生育科学研究所;
【基金】：上海市卫生局科研课题计划(20114152)
【分类号】：R737.33

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