FAM19A4基因启动子DNA甲基化对宫颈病变的诊断价值研究  

Study on the diagnostic value of FAM19A4 gene promoter DNA methylation cervical lesions

作　　者：段小令 李勤妹 黄燕春 王煜暖 陆琦 DUAN Xiao-ling;LI Qin-mei;HUANG Yan-chun;WANG Yu-nuan;LU Qi(Department of Gynecology and Obstetrics,Jinshan Hospital of Fudan University,Shanghai 201508,China)

机构地区：[1]复旦大学附属金山医院妇产科,上海201508

出　　处：《中国妇幼保健》2023年第12期2139-2143,共5页Maternal and Child Health Care of China

基　　金：上海市科学技术委员会科研项目(18JC1411104,20Y11914100);复旦大学附属金山医院青年科研启动基金项目(JYQN-LC-202101)。

摘　　要：目的探讨序列相似家族19成员A4(FAM19A4)基因启动子DNA甲基化水平在不同宫颈病变中的差异以及对宫颈癌和癌前病变的诊断价值。方法收集188例不同阶段宫颈病变的宫颈细胞样本,其中正常宫颈组65例,低度鳞状上皮内病变(LSIL)组33例,高度鳞状上皮内病变(HSIL)组56例,宫颈癌组34例。用靶向二代测序法检测FAM19A4基因启动子DNA甲基化的表达水平,分析不同组别甲基化水平差异及对宫颈病变的诊断价值。结果宫颈癌组、HSIL组、LSIL组及正常宫颈组FAM19A4基因启动子DNA甲基化水平的中位数分别为18.89、11.39、9.72、8.89,宫颈癌组明显高于HSIL组、LSIL组及正常宫颈组,差异均有统计学意义(均P<0.05)。FAM19A4基因启动子DNA甲基化水平与宫颈病变程度呈正相关,相关系数为0.521(P<0.05)。FAM19A4基因启动子DNA甲基化诊断宫颈癌的灵敏度为82.35%,特异度为86.15%,ROC曲线下面积为0.91。结论宫颈癌和HSIL患者的FAM19A4基因启动子DNA甲基化水平异常增高,该指标对宫颈癌具有一定诊断价值。Objective To investigate DNA methylation level of family with sequence similarity 19 member A4(FAM19A4)gene pro-moter in cervical lesions and the diagnostic value for cervical cancer and precancerous lesions.Methods Cervical samples of 188 patients with cervical lesions at different stages were collected,including 65 cases of normal cervix,33 cases of low-grade cervical intraepithelial le-sion(LSIL),56 cases of high-grade intraepithelial lesion(HSIL),and 34 cases of cervical cancer.FAM19A4 gene promoter DNA methyl-ation level was analyzed by targeted next generation sequencing.The differences of methylation levels between dfferent groups and the diag-nostic value were analyzed.ResultsThe medians of FAM19A4 gene promoter DNA methylation levels in cervical cancer group,HSIL group,LSIL group,and normal cervix group were 18.89,11.39,9.72,and 8.89,respectively.The median in cervical cancer group was statistically significantly higher than those in HSIL group,LSIL group,and normal cervix group(P<0.05).FAM19A4 gene promoter DNA methylation level was positively correlated with degree of cervical lesions,the correlation coefficient was 0.521(P<0.05).The sensitivity,specificity,and area under ROC curve of FAM19A4 gene promoter DNA methylation in diagnosis of cervical cancer were 82.35%,86.15%,and 0.91,respectively.Conclusion nFAM19A4 gene promoter DNA methylation levels abnormally increase in cervical cancer and HSIL,which have high diagnostic value for cervical cancer and was expected to become a new marker for cervical cancer screening.

关 键 词：宫颈癌 宫颈低度鳞状上皮内病变 宫颈高度鳞状上皮内病变 FAM19A4基因启动子DNA甲基化 

分 类 号：R737.33[医药卫生—肿瘤]