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

被引：0

作者：

Molano, Monica ^{[1
,2
]}

Machalek, Dorothy A. ^{[1
,3
]}

Phillips, Samuel ^{[1
,2
]}

Tan, Grace ^{[5
]}

Garland, Suzanne M. ^{[1
,2
,4
]}

Hawkes, David ^{[5
]}

Balgovind, Prisha ^{[1
,2
]}

Haqshenas, Reza ^{[1
,2
,4
]}

Badman, Steve G. ^{[3
]}

Bolnga, John ^{[6
,7
]}

Gabuzzi, Josephine ^{[6
,7
]}

Kombati, Zure ^{[8
]}

Munnull, Gloria M. ^{[6
,9
]}

Brotherton, Julia ML. ^{[5
]}

Saville, Marion ^{[5
]}

Kaldor, John M. ^{[3
]}

Toliman, Pamela J. ^{[3
]}

Vallely, Andrew J. ^{[3
]}

Murray, Gerald L. ^{[1
,2
,4
]}

机构：

[1] Royal Womens Hosp, Ctr Womens Infect Dis, Melbourne, Vic, Australia

[2] Murdoch Childrens Res Inst, Melbourne, Vic, Australia

[3] Univ New South Wales, Kirby Inst, Sydney, NSW, Australia

[4] Univ Melbourne, Dept Obstet & Gynaecol, Parkville, Vic, Australia

[5] Australian Ctr Prevent Cerv Canc, Melbourne, Vic, Australia

[6] Papua New Guinea Inst Med Res, Goroka, Papua N Guinea

[7] Modilon Gen Hosp, Dept Obstet & Gynaecol, Madang, Papua N Guinea

[8] Mt Hagen Prov Hosp, Dept Pathol, WHP 281, Mt Hagen, Papua N Guinea

[9] Mt Hagen Prov Hosp, Dept Obstet & Gynaecol, Mt Hagen, Papua N Guinea

来源：

TUMOUR VIRUS RESEARCH | 2024年 / 18卷

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

DNA methylation; Cervical cancer; Human papillomavirus; Diagnostic test; Epigenetics; Molecular diagnostics; HPV-POSITIVE WOMEN; SELF-SAMPLES; TRIAGE TEST; TGF-BETA; CANCER; POPULATION; EXPRESSION; GENES; IMMORTALIZATION; (PRE)CANCER;

D O I：

10.1016/j.tvr.2024.200288

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：12