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Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia
Human papillomavirus (HPV) is detected in up to 96% of anal squamous cell cancers, where screening programs needed. However, the best methodology is still undetermined. Host DNA methylation markers CADM1, MAL and miR124 have been identified in cervical disease, but not anal disease. Anal swabs varyi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894372/ https://www.ncbi.nlm.nih.gov/pubmed/35241698 http://dx.doi.org/10.1038/s41598-022-07258-5 |
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author | Phillips, Samuel Cassells, Kahli Garland, Suzanne M. Machalek, Dorothy A. Roberts, Jennifer M. Templeton, David J. Jin, Fengyi Poynten, I. Mary Hillman, Richard J. Grulich, Andrew E. Murray, Gerald L. Tabrizi, Sepehr N. Molano, Monica Cornall, Alyssa M. |
author_facet | Phillips, Samuel Cassells, Kahli Garland, Suzanne M. Machalek, Dorothy A. Roberts, Jennifer M. Templeton, David J. Jin, Fengyi Poynten, I. Mary Hillman, Richard J. Grulich, Andrew E. Murray, Gerald L. Tabrizi, Sepehr N. Molano, Monica Cornall, Alyssa M. |
author_sort | Phillips, Samuel |
collection | PubMed |
description | Human papillomavirus (HPV) is detected in up to 96% of anal squamous cell cancers, where screening programs needed. However, the best methodology is still undetermined. Host DNA methylation markers CADM1, MAL and miR124 have been identified in cervical disease, but not anal disease. Anal swabs varying by disease grade were assessed for DNA methylation of CADM1, MAL and miR124-2. Each marker was compared across disease grades, stratified by HPV and HIV status. Receiver operating characteristic curves identified the predictive value of significant gene candidates. CADM1 methylation was significantly higher in high-grade squamous intraepithelial lesions (HSIL) compared with low-grade (LSIL) (p = 0.005) or normal (p < 0.001) samples with 67.2% correctly identified as HSIL. MAL methylation was significantly (p = 0.002) increased in HSIL compared with LSIL in HIV positive participants with 79.8% correctly indicated as HSIL. Gene miR124-2, showed no difference between disease grades. Biomarkers with established diagnostic value in cervical disease have limited utility in the prediction of anal disease, with CADM1 identified as a marker with screening potential in a gay and bisexual men (GBM) population and MAL in HIV positive GBM population. New markers specific to the anal mucosa are required to improve triage of high-risk individuals. |
format | Online Article Text |
id | pubmed-8894372 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-88943722022-03-07 Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia Phillips, Samuel Cassells, Kahli Garland, Suzanne M. Machalek, Dorothy A. Roberts, Jennifer M. Templeton, David J. Jin, Fengyi Poynten, I. Mary Hillman, Richard J. Grulich, Andrew E. Murray, Gerald L. Tabrizi, Sepehr N. Molano, Monica Cornall, Alyssa M. Sci Rep Article Human papillomavirus (HPV) is detected in up to 96% of anal squamous cell cancers, where screening programs needed. However, the best methodology is still undetermined. Host DNA methylation markers CADM1, MAL and miR124 have been identified in cervical disease, but not anal disease. Anal swabs varying by disease grade were assessed for DNA methylation of CADM1, MAL and miR124-2. Each marker was compared across disease grades, stratified by HPV and HIV status. Receiver operating characteristic curves identified the predictive value of significant gene candidates. CADM1 methylation was significantly higher in high-grade squamous intraepithelial lesions (HSIL) compared with low-grade (LSIL) (p = 0.005) or normal (p < 0.001) samples with 67.2% correctly identified as HSIL. MAL methylation was significantly (p = 0.002) increased in HSIL compared with LSIL in HIV positive participants with 79.8% correctly indicated as HSIL. Gene miR124-2, showed no difference between disease grades. Biomarkers with established diagnostic value in cervical disease have limited utility in the prediction of anal disease, with CADM1 identified as a marker with screening potential in a gay and bisexual men (GBM) population and MAL in HIV positive GBM population. New markers specific to the anal mucosa are required to improve triage of high-risk individuals. Nature Publishing Group UK 2022-03-03 /pmc/articles/PMC8894372/ /pubmed/35241698 http://dx.doi.org/10.1038/s41598-022-07258-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Phillips, Samuel Cassells, Kahli Garland, Suzanne M. Machalek, Dorothy A. Roberts, Jennifer M. Templeton, David J. Jin, Fengyi Poynten, I. Mary Hillman, Richard J. Grulich, Andrew E. Murray, Gerald L. Tabrizi, Sepehr N. Molano, Monica Cornall, Alyssa M. Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia |
title | Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia |
title_full | Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia |
title_fullStr | Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia |
title_full_unstemmed | Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia |
title_short | Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia |
title_sort | gene methylation of cadm1 and mal identified as a biomarker of high grade anal intraepithelial neoplasia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894372/ https://www.ncbi.nlm.nih.gov/pubmed/35241698 http://dx.doi.org/10.1038/s41598-022-07258-5 |
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