| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Tumour Virus Research, Vol 18, Iss , Pp 200288- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2666-6790 |
| DOI: |
10.1016/j.tvr.2024.200288 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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