Application of host DNA methylation biomarkers in cervical cancer screening:key contribution of ZNF671 and evaluation of a combined diagnostic model
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1School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515 ; 2.School of Engineering,ChinaPharmaceutical University,Nanjing 210009 ; 3.Department of Clinical Pharmacy,General Hospital of Eastern TheaterCommand,Nanjing 210002 ,China

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    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.

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WANG Yunge, LIU Yunlong, WANG Lingfei, HU Wenjing, ZHOU Guohua, WU Haiping. Application of host DNA methylation biomarkers in cervical cancer screening:key contribution of ZNF671 and evaluation of a combined diagnostic model[J].,2025,(9):1242-1250.

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  • Received:May 05,2025
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  • Online: September 11,2025
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