DNA methylation signatures of cervical pre-invasive and invasive disease: an epigenome-wide association study
Author(s)
Type
Journal Article
Abstract
Epigenetic alterations are essential in the development of cancers, while epigenome-wide exploration in cervical cancer has been limited. In this epigenome-wide association study (EWAS) we explore differential DNA methylation signatures associated with CIN (cervical intraepithelial neoplasia) grade 3 and cervical cancer to better understand potential drivers and biomarkers of cervical carcinogenesis. 247 women were recruited between 2014 and 2020 (N = 119 benign, N = 74 CIN3/CGIN [cervical glandular intraepithelial neoplasia] and N = 54 cancer). Methylation signatures were obtained from exfoliated cervical cells and sequenced using the Illumina 850 k array. Logistic regression and conditional analyses were used to test for independent associations between Cytosine-phosphate-Guanine (CpG) sites and case–control status, with adjustment for batch, chip, age, and human papillomavirus (HPV) status. 409 CpG sites were strongly associated with CIN3/cancer (p-value <5 × 10−8). Following conditional analysis, two CpG sites located in PAX1 (cg16767801) and NREP-AS1 genes (cg23642047) were independently associated with case status, yielding an area under the curve (AUC) of 0.92 (AUC = 0.97 for invasive disease). In a validation dataset (CIN3 only) PAX1/NREP-AS1 yielded a combined AUC of 0.77. Methylation markers offer promise for use in cervical screening, particularly as triage tests and self-sampling. We have identified a novel combined methylation marker that offers a high accuracy for the detection of CIN3 or worse.
Date Issued
2025-07-15
Date Acceptance
2025-02-27
Citation
International Journal of Cancer, 2025, 157 (2), pp.305-316
ISSN
0020-7136
Publisher
Wiley
Start Page
305
End Page
316
Journal / Book Title
International Journal of Cancer
Volume
157
Issue
2
Copyright Statement
© 2025 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
10.1002/ijc.35406
Publication Status
Published
Date Publish Online
2025-03-10