高危型人乳头瘤病毒感染患者宫颈脱落细胞JAM3/PAX1高甲基化诊断宫颈高级别病变  

High-grade cervical lesions diagnosed by JAM3/PAX1 methylation in high-risk human papillomavirus-infected patients

作　　者：李翔[1] 贺斯黎 赵行平 孙丹 吴思 徐大宝[1] 李颖佳[2] LI Xiang;HE Sili;ZHAO Xingping;SUN Dan;WU Si;XU Dabao;LI Yingjia(Department of Gynecology,Third Xiangya Hospital,Central South University,Changsha 410013;Department of Clinical Laboratory,Third Xiangya Hospital,Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅三医院妇科,长沙410013 [2]中南大学湘雅三医院检验科,长沙410013

出　　处：《中南大学学报（医学版）》2023年第12期1820-1829,共10页Journal of Central South University ：Medical Science

基　　金：湖南省临床医疗技术创新引导项目(2020SK53604)。

摘　　要：目的:传统的宫颈癌筛查手段——高危型人乳头瘤病毒(high-risk human papillomavirus,hrHPV)和宫颈脱落细胞学检测存在局限性。本研究通过检测宫颈脱落细胞中连接黏附分子3(junctional adhesion molecule 3,JAM3)/配对盒基因1(paired box gene 1,PAX1)高甲基化水平,并将其与液基薄层细胞学(liquid based cytology,LBC)进行比较,评价JAM3/PAX1甲基化对于宫颈高级别病变的诊断能力,以探索新的宫颈高级别病变的诊断模式,实现宫颈高级别病变“精准筛查”的目的。方法:回顾性收集2021年6月至2022年6月在中南大学湘雅三医院妇科阴道镜门诊接受检查的患者共136例,包括宫颈非高级别病变122例,高级别病变14例。研究的变量包括:基本临床信息(年龄、体重指数、是否绝经)、LBC、hrHPV、宫颈组织病理、阴道微生态结果、阴道镜结果(宫颈转化区类型)、JAM3(ΔCtJ)和PAX1(ΔCtP)基因甲基化的ΔCt值。首先通过logistic回归分析筛选影响宫颈高级别病变的影响因素,并进行相关性分析,然后用差异有统计学意义的变量构建条件推断树模型。结果:Logistic回归分析提示高级别宫颈病变组与非高级别宫颈病变组的PAX1与JAM3基因甲基化ΔCt值以及LBC检测结果差异均有统计学意义(均P<0.05)。相关性分析发现,宫颈病理结果与ΔCtP(r=-0.360,P<0.001)、ΔCtJ(r=-0.448,P<0.001)、LBC(r=-0.305,P<0.001)、菌群多样性(r=-0.183,P=0.037)呈负相关。条件推断树显示:当ΔCtJ>10.13时,全部为宫颈非高级别病变的患者;当ΔCtP>6.22时,非高级别病变的患者有117例,占97.5%,高级别病变者仅3例,占2.5%。ΔCtJ>8.61且LBC为不明确的非鳞状上皮细胞(atypical squamous cell of undetermined significance,ASC-US)或未见上皮内病变细胞时,105例(99.1%)为宫颈非高级别病变的患者,仅1例(0.9%)检出为高级别病变;当LBC结果为高级别病变时,仅9例患者检出高级别病变,3例检出非高级别病变;而当LBC提示低Objective:Currently,traditional cervical cancer screening methods,such as high-risk human papillomavirus testing and liquid based cytology(LBC),still possess limitations.This study aims to identify new diagnostic biomarkers to achieve the goal of“precision screening”via exploring the clinical value of DNA methylation[ΔCtP:paired box gene 1(PAX1)andΔCtJ:junctional adhesion molecule 3(JAM3)]detection in cervical exfoliated cells for the diagnosis of high-grade cervical lesions.Methods:A total of 136 patients who underwent gynecological examinations in the vaginal room of the Department of Gynecology at the Third Xiangya Hospital of Central South University from June 2021 to June 2022 were retrospectively studied.Among them,122 patients had non-high-grade cervical lesions,and 14 patients had high-grade cervical lesions.The variables included general information(age,body mass index,and menopause status),LBC,high-risk human papillomavirus,cervical tissue pathology,vaginal examination results,and theΔCt values of JAM3 and PAX1 gene methylation.Logistic regression analysis was used to identify the factors affecting the diagnosis of high-grade cervical lesions,followed by correlation analysis and construction of a conditional inference tree model.Results:Logistic regression analysis showed that the methylationΔCt values of PAX1 and JAM3 genes and LBC detection results were statistically significant between the high-grade cervical lesions group and the non-high-grade cervical lesions group(all P<0.05).Correlation analysis revealed a negative correlation between cervical pathological changes andΔCtP(r=-0.36,P<0.001),ΔCtJ(r=-0.448,P<0.001),LBC(r=-0.305,P<0.001),or bacterial diversity(r=-0.183,P=0.037).The conditional inference tree showed that whenΔCtJ>10.13,all of patients had non-high-grade cervical lesions,whileΔCtP>6.22,the number of non-high-grade lesions accounted for 97.5%(117/120),and high-grade lesions accounted for only 2.5%(3/120).WhenΔCtJ>8.61 and LBC were atypical squamous cell of undetermined sign

关 键 词：宫颈病变 DNA甲基化 连接黏附分子3 配对盒基因1 条件推断树 

分 类 号：R737.33[医药卫生—肿瘤]