Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia
Abstract 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 sw...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-07258-5 |
| _version_ | 1818915626377281536 |
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| author | Samuel Phillips Kahli Cassells Suzanne M. Garland Dorothy A. Machalek Jennifer M. Roberts David J. Templeton Fengyi Jin I. Mary Poynten Richard J. Hillman Andrew E. Grulich Gerald L. Murray Sepehr N. Tabrizi Monica Molano Alyssa M. Cornall SPANC team |
| author_facet | Samuel Phillips Kahli Cassells Suzanne M. Garland Dorothy A. Machalek Jennifer M. Roberts David J. Templeton Fengyi Jin I. Mary Poynten Richard J. Hillman Andrew E. Grulich Gerald L. Murray Sepehr N. Tabrizi Monica Molano Alyssa M. Cornall SPANC team |
| author_sort | Samuel Phillips |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-20T00:05:16Z |
| format | Article |
| id | doaj.art-4a0a27fd81c24146bb3e5538ff3eb2a4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T00:05:16Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4a0a27fd81c24146bb3e5538ff3eb2a42022-12-21T20:00:39ZengNature PortfolioScientific Reports2045-23222022-03-0112111110.1038/s41598-022-07258-5Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasiaSamuel Phillips0Kahli Cassells1Suzanne M. Garland2Dorothy A. Machalek3Jennifer M. Roberts4David J. Templeton5Fengyi Jin6I. Mary Poynten7Richard J. Hillman8Andrew E. Grulich9Gerald L. Murray10Sepehr N. Tabrizi11Monica Molano12Alyssa M. Cornall13SPANC teamDepartment of Obstetrics and Gynecology, University of MelbourneDepartment of Obstetrics and Gynecology, University of MelbourneDepartment of Obstetrics and Gynecology, University of MelbourneCentre Women’s Infectious Diseases Research, The Royal Women’s HospitalDouglass Hanly Moir PathologyHIV Epidemiology and Prevention Program, The Kirby Institute, University of New South WalesHIV Epidemiology and Prevention Program, The Kirby Institute, University of New South WalesHIV Epidemiology and Prevention Program, The Kirby Institute, University of New South WalesHIV Epidemiology and Prevention Program, The Kirby Institute, University of New South WalesHIV Epidemiology and Prevention Program, The Kirby Institute, University of New South WalesDepartment of Obstetrics and Gynecology, University of MelbourneDepartment of Obstetrics and Gynecology, University of MelbourneCentre Women’s Infectious Diseases Research, The Royal Women’s HospitalDepartment of Obstetrics and Gynecology, University of MelbourneAbstract 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.https://doi.org/10.1038/s41598-022-07258-5 |
| spellingShingle | Samuel Phillips Kahli Cassells Suzanne M. Garland Dorothy A. Machalek Jennifer M. Roberts David J. Templeton Fengyi Jin I. Mary Poynten Richard J. Hillman Andrew E. Grulich Gerald L. Murray Sepehr N. Tabrizi Monica Molano Alyssa M. Cornall SPANC team Gene methylation of CADM1 and MAL identified as a biomarker of high grade anal intraepithelial neoplasia Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-022-07258-5 |
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