DNA Methylation Markers Have Universal Prognostic Value for Anal Cancer Risk in HIV-negative and HIV-positive Individuals

Overview

Journal Mol Oncol

Specialties Molecular Biology
Oncology

Date 2021 Feb 13

PMID 33580586

Citations 13

Authors

Ramon P van der Zee

Carel J M van Noesel

Ivonne Martin

Timo J Ter Braak

Danielle A M Heideman

Henry J C de Vries

Jan M Prins

Renske D M Steenbergen

Affiliations

Soon will be listed here.

Abstract

Anal cancer has increasing incidence and is preceded by high-grade anal intraepithelial neoplasia (HGAIN; AIN2-3). Previously, we identified and validated several methylation markers for accurate detection of anal cancer and HGAIN with cancer risk in HIV-positive (HIV+) men who have sex with men (MSM). This study aimed to evaluate these markers in HIV-negative risk groups. A cross-sectional series of 176 tissue samples of anal cancer, AIN3, AIN2, AIN1 and control biopsies obtained in HIV-negative women and men was tested for six methylation markers (ASCL1, LHX8, SST, WDR17, ZIC1 and ZNF582). Accuracy for detection of AIN3 and cancer (AIN3+) was determined by univariable and multivariable mixed-effect ordinal logistic regression. Methylation levels of all markers increased with increasing severity of disease (P < 0.0001) and were comparable to results in HIV+ MSM. All markers showed high accuracy for AIN3+ detection [area under the curve (AUC): 0.83-0.86]. The optimal marker panel (ASCL1 and ZIC1; AUC = 0.85 for AIN3+) detected 98% of cancers at 79% specificity. In conclusion, DNA methylation markers show a high diagnostic performance for AIN3+ detection in HIV+ and HIV-negative risk groups, justifying broad application of methylation analysis for anal cancer prevention programmes.

Citing Articles

Diagnostic Performance of Host and Viral DNA Methylation Analysis in the Identification of Anal Intraepithelial Neoplasia and Cancer: Systematic Review and Meta-Analysis.

Muresu N, Puci M, Sotgiu G, Sechi I, Cossu A, Usai M Healthcare (Basel). 2024; 12(19).

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Screening of Anal HPV Precancerous Lesions: A Review after Last Recommendations.

Natale A, Brunetti T, Orioni G, Gaspari V J Clin Med. 2024; 13(17).

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Epigenetic reprogramming in gastrointestinal cancer: biology and translational perspectives.

Wang Y, Zhang M, Xu J, Zheng L, Liu P, Chen J MedComm (2020). 2024; 5(9):e670.

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Screening for precancerous anal lesions linked to human papillomaviruses: French recommendations for clinical practice.

Spindler L, Etienney I, Abramowitz L, de Parades V, Pigot F, Siproudhis L Tech Coloproctol. 2024; 28(1):23.

PMID: 38198036 PMC: 10781838. DOI: 10.1007/s10151-023-02899-8.

Analytical validation and diagnostic performance of the ASCL1/ZNF582 methylation test for detection of high-grade anal intraepithelial neoplasia and anal cancer.

Rozemeijer K, Dias Goncalves Lima F, Ter Braak T, Hesselink A, Prins J, de Vries H Tumour Virus Res. 2023; 17:200275.

PMID: 38160718 PMC: 10821616. DOI: 10.1016/j.tvr.2023.200275.

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