Higher levels of host-cell DNA methylation markers ZNF582 and ASCL1 on anal smears are predictive for progression to anal cancer in patients with previous high-grade lesions.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-24 DOI:10.1016/j.ebiom.2025.105936

Valentine Marie Ferré, Axelle Dupont, Mélanie Draullette, Emy Valette, Gilles Collin, Margot Bucau, Laurent Siproudhis, Ghislain Staumont, Carine Roy, Albertus Theodorus Hesselink, Dominique Bouchard, Sylvie Radenne, Lucas Spindler, Anas Naji, Christine Bergeron, Anne Couvelard, Diane Descamps, Renske D M Steenbergen, Charlotte Charpentier, Laurent Abramowitz

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引用次数: 0

Abstract

Background: French and International anal cancer screening recommendations for at-risk populations, published in 2024, are based on cytology and/or high-risk human papillomavirus (HPV) detection on anal smears. Biological markers to triage the patients most at-risk for anal cancer are crucial in prioritising patients needing high-resolution anoscopy consultations, which are frequently overwhelmed.

Methods: The AIN3 cohort is a French national multicenter study including patients with a history of high-grade anal lesions (AIN3). Patients were followed-up for at least 3 years, with anal smears and clinical examinations performed yearly. Levels of ZNF582 and ASCL1 gene methylation were quantified using real-time PCR on anal smears collected at the time of inclusion.

Findings: Overall, 514 anal smears were contributive for host-cell DNA methylation analysis. Patients' mean age was 50.8 years and 40% were women. Among the 41% who were living with HIV, 91% were men. Median follow-up duration was 48 months, and 22 patients (4%) developed anal cancer during follow-up. Higher methylation levels of ZNF582 and ASCL1 were significantly associated with high-grade squamous cell intraepithelial lesion (HSIL) cytology, p16-Ki67 dual-staining positivity, and high-risk HPV and HPV16 positivity on the same anal smear. Both methylation markers showed an AUC of 0.72 for discrimination between HSIL and non-HSIL cytology on the same anal smear. Higher methylation levels of both markers were significantly associated with evolution to anal cancer in univariate and multivariable analyses adjusted for age and HIV status (p < 0.001). When assessing the AUC over 1 and 3 years of follow-up, methylation markers demonstrated superior predictive value for anal cancer compared to other markers.

Interpretation: We have demonstrated the predictive value of host-cell DNA methylation marker levels in anal smears with regard to evolution to anal cancer in a very high-risk population.

Funding: This study was funded by the Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) I Maladies Infectieuses Emergentes.

查看原文本刊更多论文

肛门涂片上较高水平的宿主细胞DNA甲基化标记物ZNF582和ASCL1可预测既往高级别病变患者进展为肛门癌。

背景：法国和国际于2024年发布的针对高危人群的肛门癌筛查建议是基于细胞学和/或肛门涂片中高危人乳头瘤病毒（HPV）的检测。对于那些需要高分辨率肛门镜检查的患者来说，鉴别患肛门癌风险最高的患者的生物标记是至关重要的。方法：AIN3队列是一项法国国家多中心研究，包括有高度肛门病变史（AIN3）的患者。患者随访至少3年，每年进行肛门涂片和临床检查。采用实时荧光定量PCR对纳入时收集的肛门涂片进行ZNF582和ASCL1基因甲基化水平的定量分析。结果：总体而言，514份肛门涂片有助于宿主细胞DNA甲基化分析。患者平均年龄50.8岁，女性占40%。在41%的艾滋病毒感染者中，91%是男性。中位随访时间为48个月，22例（4%）患者在随访期间发生肛门癌。高甲基化水平的ZNF582和ASCL1与高级别鳞状细胞上皮内病变（HSIL）细胞学、p16-Ki67双染色阳性以及同一肛门涂片上高危HPV和HPV16阳性显著相关。两种甲基化标记在同一肛门涂片上区分HSIL和非HSIL细胞学的AUC均为0.72。在调整了年龄和HIV状态的单变量和多变量分析中，这两种标记物较高的甲基化水平与肛门癌的进化显著相关（p < 0.001）。在评估随访1年和3年的AUC时，与其他标志物相比，甲基化标志物对肛门癌的预测价值更高。解释：我们已经证明了肛门涂片中宿主细胞DNA甲基化标记物水平对高危人群中肛门癌进化的预测价值。资助：本研究由国家艾滋病和艾滋病毒病及突发疾病感染研究机构资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.