DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging
Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methy...
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Elsevier
2024-12-01
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| Series: | Tumour Virus Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666679024000120 |
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| author | Monica Molano Dorothy A. Machalek Samuel Phillips Grace Tan Suzanne M. Garland David Hawkes Prisha Balgovind Reza Haqshenas Steve G. Badman John Bolnga Josephine Gabuzzi Zure Kombati Gloria M. Munnull Julia ML. Brotherton Marion Saville John M. Kaldor Pamela J. Toliman Andrew J. Vallely Gerald L. Murray |
| author_facet | Monica Molano Dorothy A. Machalek Samuel Phillips Grace Tan Suzanne M. Garland David Hawkes Prisha Balgovind Reza Haqshenas Steve G. Badman John Bolnga Josephine Gabuzzi Zure Kombati Gloria M. Munnull Julia ML. Brotherton Marion Saville John M. Kaldor Pamela J. Toliman Andrew J. Vallely Gerald L. Murray |
| author_sort | Monica Molano |
| collection | DOAJ |
| description | Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea.Methylation of EPB41L3 (1–6 CpG-sites), hTERT (1–10 CpG-sites) and FAM19A4 (1–5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously.In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity].Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%.In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation. |
| format | Article |
| id | doaj-art-ac0c71d30e3949adb60b51b194c457ea |
| institution | Kabale University |
| issn | 2666-6790 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Tumour Virus Research |
| spelling | doaj-art-ac0c71d30e3949adb60b51b194c457ea2024-12-15T06:17:19ZengElsevierTumour Virus Research2666-67902024-12-0118200288DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averagingMonica Molano0Dorothy A. Machalek1Samuel Phillips2Grace Tan3Suzanne M. Garland4David Hawkes5Prisha Balgovind6Reza Haqshenas7Steve G. Badman8John Bolnga9Josephine Gabuzzi10Zure Kombati11Gloria M. Munnull12Julia ML. Brotherton13Marion Saville14John M. Kaldor15Pamela J. Toliman16Andrew J. Vallely17Gerald L. Murray18Centre for Women's Infectious Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia; Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Corresponding author.Centre for Women's Infectious Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia; The Kirby Institute, University of New South Wales, Sydney, NSW, AustraliaCentre for Women's Infectious Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia; Murdoch Children's Research Institute, Melbourne, Victoria, AustraliaAustralian Centre for the Prevention of Cervical Cancer, Melbourne, Victoria, AustraliaCentre for Women's Infectious Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia; Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, AustraliaAustralian Centre for the Prevention of Cervical Cancer, Melbourne, Victoria, AustraliaCentre for Women's Infectious Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia; Murdoch Children's Research Institute, Melbourne, Victoria, AustraliaCentre for Women's Infectious Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia; Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, AustraliaThe Kirby Institute, University of New South Wales, Sydney, NSW, AustraliaPapua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Department of Obstetrics and Gynaecology, Modilon General Hospital, Madang, Papua New GuineaPapua New Guinea Institute of Medical Research, Goroka, Papua New Guinea; Department of Obstetrics and Gynaecology, Modilon General Hospital, Madang, Papua New GuineaDepartment of Pathology, Mt Hagen Provincial Hospital, WHP 281, Papua New GuineaDepartment of Obstetrics and Gynaecology, Mt Hagen Provincial Hospital, Mount Hagen, Papua New Guinea; Papua New Guinea Institute of Medical Research, Goroka, Papua New GuineaAustralian Centre for the Prevention of Cervical Cancer, Melbourne, Victoria, AustraliaAustralian Centre for the Prevention of Cervical Cancer, Melbourne, Victoria, AustraliaThe Kirby Institute, University of New South Wales, Sydney, NSW, AustraliaThe Kirby Institute, University of New South Wales, Sydney, NSW, AustraliaThe Kirby Institute, University of New South Wales, Sydney, NSW, AustraliaCentre for Women's Infectious Diseases, The Royal Women's Hospital, Melbourne, Victoria, Australia; Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, AustraliaGlobal methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea.Methylation of EPB41L3 (1–6 CpG-sites), hTERT (1–10 CpG-sites) and FAM19A4 (1–5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously.In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity].Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%.In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.http://www.sciencedirect.com/science/article/pii/S2666679024000120DNA methylationCervical cancerHuman papillomavirusDiagnostic testEpigeneticsMolecular diagnostics |
| spellingShingle | Monica Molano Dorothy A. Machalek Samuel Phillips Grace Tan Suzanne M. Garland David Hawkes Prisha Balgovind Reza Haqshenas Steve G. Badman John Bolnga Josephine Gabuzzi Zure Kombati Gloria M. Munnull Julia ML. Brotherton Marion Saville John M. Kaldor Pamela J. Toliman Andrew J. Vallely Gerald L. Murray DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging Tumour Virus Research DNA methylation Cervical cancer Human papillomavirus Diagnostic test Epigenetics Molecular diagnostics |
| title | DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging |
| title_full | DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging |
| title_fullStr | DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging |
| title_full_unstemmed | DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging |
| title_short | DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging |
| title_sort | dna methylation at individual cpg sites of epb41l3 htert and fam19a4 are useful for detection of cervical high grade squamous intraepithelial lesions hsil or worse analysis of individual cpg sites outperforms averaging |
| topic | DNA methylation Cervical cancer Human papillomavirus Diagnostic test Epigenetics Molecular diagnostics |
| url | http://www.sciencedirect.com/science/article/pii/S2666679024000120 |
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