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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

Authors :
Molano, M
Machalek, DA
Phillips, S
Tan, G
Garland, SM
Hawkes, D
Balgovind, P
Haqshenas, R
Badman, SG
Bolnga, J
Gabuzzi, J
Kombati, Z
Munnull, GM
Brotherton, JML
Saville, M
Kaldor, JM
Toliman, PJ
Vallely, AJ
Murray, GL
Molano, M
Machalek, DA
Phillips, S
Tan, G
Garland, SM
Hawkes, D
Balgovind, P
Haqshenas, R
Badman, SG
Bolnga, J
Gabuzzi, J
Kombati, Z
Munnull, GM
Brotherton, JML
Saville, M
Kaldor, JM
Toliman, PJ
Vallely, AJ
Murray, GL
Publication Year :
2024

Abstract

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.

Details

Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1456029197
Document Type :
Electronic Resource