南京医科大学学报（自然科学版）2025，Vol.45Issue(9)：1242-1250,9.DOI:10.7655/NYDXBNSN250520
宿主DNA甲基化标志物在宫颈癌筛查中的应用:ZNF671的关键贡献与联合模型评价
Application of host DNA methylation biomarkers in cervical cancer screening:key contribution of ZNF671 and evaluation of a combined diagnostic model
摘要
Abstract
Objective:To investigate the diagnostic value of DNA methylation levels of the host genes SOX1,JAM3,ZNF671,and DLX1 for cervical intraepithelial neoplasia grade 2 or worse(CIN2+)in women positive for human papillomavirus(HPV)16/18,and to construct a risk stratification model to optimize cervical cancer screening strategies.Methods:Cervical exfoliated cell samples were collected from HPV16/18-positive women attending the General Hospital of Eastern Theater Command between April 2023 and May 2024.DNA methylation levels of the four host genes were measured using bisulfite-converted pyrosequencing.Samples were grouped according to histopathological diagnosis(normal,low-grade histology,high-grade histology,cancer),and intergroup methylation differences were compared.Logistic regression was used to construct a predictive model for CIN2+,and its diagnostic performance was assessed in both training and testing datasets.Results:The methylation levels of all four host genes increased progressively with lesion severity and were significantly higher in the CIN2+group than in the CIN1-group(P<0.001),demonstrating high diagnostic specificity.Among them,ZNF671 exhibited the best performance as a single biomarker,with an area under the curve(AUC)of 0.741.The combined model of ZNF671 and SOX1 achieved AUCs of 0.801 and 0.745 in the training and testing sets,respectively,with a specificity up to 87%,outperforming any individual gene.Conclusion:The DNA methylation levels of SOX1,JAM3,ZNF671,and DLX1 are closely associated with the severity of cervical lesions and exhibit potential value for triage.In particular,ZNF671 shows strong predictive performance for CIN2+in HPV16/18-positive women,and may serve as an auxiliary biomarker for identifying precancerous lesions.The combined model incorporating SOX1 further improves diagnostic accuracy.关键词
宫颈癌/DNA甲基化/ZNF671/分诊策略/HPV16/18Key words
cervical cancer/DNA methylation/ZNF671/triage strategy/HPV16/18分类
医药卫生引用本文复制引用
王韫格,刘云龙,王玲菲,户文静,周国华,武海萍..宿主DNA甲基化标志物在宫颈癌筛查中的应用:ZNF671的关键贡献与联合模型评价[J].南京医科大学学报（自然科学版）,2025,45(9):1242-1250,9.基金项目
国家自然科学基金(22474058,61901527) （22474058,61901527）
江苏省"十四五"医学重点学科建设单位(JSDW202250) （JSDW202250）
医院临床诊疗新技术项目(22LCZLXJS15) （22LCZLXJS15）
