Details

Autor(en) / Beteiligte

• van der Zee, Ramon P.
• van Noesel, Carel J.M.
• Martin, Ivonne
• ter Braak, Timo J.
• Heideman, Daniëlle A.M.
• de Vries, Henry J.C.
• Prins, Jan M.
• Steenbergen, Renske D.M.

Titel

DNA methylation markers have universal prognostic value for anal cancer risk in HIV‐negative and HIV‐positive individuals

Ist Teil von

• Molecular oncology, 2021-11, Vol.15 (11), p.3024-3036

Ort / Verlag

United States: John Wiley & Sons, Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley Online Library Journals【Remote access available】

Beschreibungen/Notizen

• 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. Host cell DNA methylation plays a role in anal carcinogenesis in HIV‐negative (HIV‐neg) and HIV‐positive (HIV+) individuals, including men who have sex with men (MSM). Methylation levels are increased in high‐grade anal intraepithelial neoplasia at risk of progression towards anal cancer, making methylation markers promising prognostic biomarkers.