Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus–Positive Men by Validated Methylation Markers Associated With Progression to Cancer.
| Autor: | Zee, Ramon P van der, Richel, Olivier, Noesel, Carel J M van, Ciocănea-Teodorescu, Iuliana, Splunter, Annina P van, Braak, Timo J ter, Nathan, Mayura, Cuming, Tamzin, Sheaff, Michael, Kreuter, Alexander, Meijer, Chris J L M, Quint, Wim G V, Vries, Henry J C de, Prins, Jan M, Steenbergen, Renske D M |
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| Předmět: |
HIV infection complications
DISEASE progression HIV-positive persons BIOPSY CROSS-sectional method MULTIPLE regression analysis ANAL tumors RISK assessment DNA methylation SEVERITY of illness index DESCRIPTIVE statistics TUMOR markers POLYMERASE chain reaction ANAL intraepithelial neoplasia DISEASE risk factors |
| Zdroj: | Clinical Infectious Diseases; 6/15/2021, Vol. 72 Issue 12, p2154-2163, 10p |
| Abstrakt: | Background High-grade anal intraepithelial neoplasia (HGAIN; AIN2–3) is highly prevalent in HIV+ men, but only a minority of these lesions progress towards cancer. Currently, cancer progression risk cannot be established; therefore, no consensus exists on whether HGAIN should be treated. This study aimed to validate previously identified host cell DNA methylation markers for detection and cancer risk stratification of HGAIN. Methods A large independent cross-sectional series of 345 anal cancer, AIN3, AIN2, AIN1, and normal control biopsies of HIV+ men was tested for DNA methylation of 6 genes using quantitative methylation-specific PCR. We determined accuracy for detection of AIN3 and cancer (AIN3+) by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Methylation levels were assessed in a series of 10 anal cancer cases with preceding HGAIN at similar anatomic locations, and compared with the cross-sectional series. Results Methylation levels of all genes increased with increasing severity of disease (P < .05). HGAIN revealed a heterogeneous methylation pattern, with a subset resembling cancer. ZNF582 showed highest accuracy (AUC = 0.88) for AIN3+ detection, slightly improved by addition of ASCL1 and SST (AUC = 0.89), forming a marker panel. In the longitudinal series, HGAIN preceding cancer displayed high methylation levels similar to cancers. Conclusions We validated the accuracy of 5 methylation markers for the detection of anal (pre-) cancer. High methylation levels in HGAIN were associated with progression to cancer. These markers provide a promising tool to identify HGAIN in need of treatment, preventing overtreatment of HGAIN with a low cancer progression risk. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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