宫颈脱落细胞中FAM19A4基因启动子甲基化的检测分析  

Detection and analysis of FAM19A4 promoter methylation in cervical exfoliated cells

作　　者：王三锋[1] 布俏雯 张亮[1] 马健伍 恒英 罗家祺 罗喜平[1] Wang Sanfeng;Bu Qiaowen;Zhang Liang;Ma Jianivu;Heng Ying;Luo Jiaqi;Luo Xiping(Guangdong Women and Children's Hospital, Guangzhou 510010, China)

机构地区：[1]广东省妇幼保健院妇科,广州510010

出　　处：《中华医学杂志》2019年第25期1963-1967,共5页National Medical Journal of China

基　　金：广东省科技计划(2017ZC0285).

摘　　要：目的探讨宫颈脱落细胞中FAM19A4基因启动子甲基化检测在宫颈癌筛查中的临床价值。方法收集2017年8至12月间在广东省妇幼保健院就诊,经病理学确诊为不同宫颈病变的高危型HPV(HR-HPV)感染患者,共162例。采取双探针荧光定量PCR检测不同级别宫颈病变的宫颈脱落细胞中的FAM19A4基因启动子甲基化表达情况,并通过诊断试验计算该基因甲基化在预测宫颈HSIL及以上病变的价值。结果(1)宫颈脱落细胞中FAM19A4甲基化阳性率随着宫颈病变严重程度增加,在正常宫颈/宫颈炎、宫颈低度鳞状上皮内病变(LSIL)、宫颈高分化鳞状上皮内病变(HSIL)和宫颈癌中分别为:7.69%(4/52),34.62%(9/26),55.56%(20/36),95.83%(46/48)(P<0.05)。(2)FAM19A4甲基化检出率在宫颈癌不同年龄段、病理学类型、临床分期、肿瘤大小及淋巴结转移状态间差异均无统计学意义(均P>0.05)。(3)FAM19A4甲基化在检测宫颈HSIL和≥HSIL病变时的特异度及阳性预测值最佳,曲线下面积分别为0.69和0.84;联合HPV16/18分型检测明显提高灵敏度。结论宫颈脱落细胞FAM19A4基因启动子甲基化检测在发现宫颈≥HSIL病变中具有较高的临床价值;当联合HPV16/18分型检测后,能更灵敏地检测出宫颈≥HSIL病变。Objective To investigate the cinical value of FAM19A4promoter methylation in cervicalexfoliated cells for triage of cervical cancer. MethodsA total of 162 high-risk HPV-infected patients who were pathologically confirmed as different cervical lesions from August 2017 to December 2017 were collected in Guangdong Women and Children Hospital. Taqman probe-based quantitative PCR (qPCR) was used to detect the methylation of FAM19A4 promoterin different grades of cervical lesions, and the value of FAM19A4 methylation in predicting cervical HSIL and the above lesions was calculated by diagnostic test. Results(1)The positive rates of FAM19A4 methylation in cervical exfoliated cells increased with the severity of cervical lesions, which were 7.69%(4/52), 34.62%(9/26), 55.56%(20/36), 95.83%(46/48) in normal cervix/cervicitis, cervical LSIL, HSIL, and cervical cancer, respectively(P<0.05).(2)There was no significant difference in the detection rates of FAM19A4 methylation between different age groups, pathological types, clinical stage, tumor size and lymph node metastasis status (P>0.05).(3) The specificity and positive predictive value of FAM19A4 methylation in detecting cervical HSIL alone and ≥HSIL lesions were the optimal, with the AUC of 0.69 and 0.84, respectively. When combined with HPV16/18 genotyping, the sensitivity was significantly improved. ConclusionsThe detection of FAM19A4 promoter methylation in cervical exfoliated cells has a high clinical value of discriminating ≥HSIL lesions;and the cotest of methylated FAM19A4 and HPV16/18 genotyping can identify ≥HSIL lesions more sensitively.

关 键 词：宫颈脱落细胞 FAM19A4 DNA甲基化 宫颈癌筛查 

分 类 号：R737.33[医药卫生—肿瘤]