EPB41L3、HTERT和FAM19A4的单个CpG位点的DNA甲基化有助于检测宫颈高级别鳞状上皮内病变(HSIL)或更严重的病变:对单个 CpG 位点的分析优于平均分析。

IF 4.7 Q1 VIROLOGY
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
{"title":"EPB41L3、HTERT和FAM19A4的单个CpG位点的DNA甲基化有助于检测宫颈高级别鳞状上皮内病变(HSIL)或更严重的病变:对单个 CpG 位点的分析优于平均分析。","authors":"Monica Molano ,&nbsp;Dorothy A. Machalek ,&nbsp;Samuel Phillips ,&nbsp;Grace Tan ,&nbsp;Suzanne M. Garland ,&nbsp;David Hawkes ,&nbsp;Prisha Balgovind ,&nbsp;Reza Haqshenas ,&nbsp;Steve G. Badman ,&nbsp;John Bolnga ,&nbsp;Josephine Gabuzzi ,&nbsp;Zure Kombati ,&nbsp;Gloria M. Munnull ,&nbsp;Julia ML. Brotherton ,&nbsp;Marion Saville ,&nbsp;John M. Kaldor ,&nbsp;Pamela J. Toliman ,&nbsp;Andrew J. Vallely ,&nbsp;Gerald L. Murray","doi":"10.1016/j.tvr.2024.200288","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p><p>Methylation of <em>EPB41L3</em> (1–6 CpG-sites), <em>hTERT</em> (1–10 CpG-sites) and <em>FAM19A4</em> (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 <em>FAM19A4</em> directed to the first exon region not explored previously.</p><p>In clinician-collected samples, methylation at CpG-sites 4 and 5 of <em>EPB41L3</em> were the best HSIL predictors (AUC &gt;0.83) and CpG-site 4 for cancer (0.925). Combination of <em>EPB41L3</em> sites 2/4 plus <em>FAM19A4</em> site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity].</p><p>Methylation at CpG-site 5 of <em>FAM19A4</em> was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of <em>FAM19A4</em> for cancer (0.77). Combined, <em>FAM19A4</em> site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%.</p><p>In conclusion, methylation at individual CpG-sites of <em>EPB41L3</em> and <em>FAM19A4</em> outperformed global analysis and improved HSIL+ detection, warranting further investigation.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000120/pdfft?md5=211b8be54b2e08277c81b68123f37b1d&pid=1-s2.0-S2666679024000120-main.pdf","citationCount":"0","resultStr":"{\"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\",\"authors\":\"Monica Molano ,&nbsp;Dorothy A. Machalek ,&nbsp;Samuel Phillips ,&nbsp;Grace Tan ,&nbsp;Suzanne M. Garland ,&nbsp;David Hawkes ,&nbsp;Prisha Balgovind ,&nbsp;Reza Haqshenas ,&nbsp;Steve G. Badman ,&nbsp;John Bolnga ,&nbsp;Josephine Gabuzzi ,&nbsp;Zure Kombati ,&nbsp;Gloria M. Munnull ,&nbsp;Julia ML. Brotherton ,&nbsp;Marion Saville ,&nbsp;John M. Kaldor ,&nbsp;Pamela J. Toliman ,&nbsp;Andrew J. Vallely ,&nbsp;Gerald L. Murray\",\"doi\":\"10.1016/j.tvr.2024.200288\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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.</p><p>Methylation of <em>EPB41L3</em> (1–6 CpG-sites), <em>hTERT</em> (1–10 CpG-sites) and <em>FAM19A4</em> (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 <em>FAM19A4</em> directed to the first exon region not explored previously.</p><p>In clinician-collected samples, methylation at CpG-sites 4 and 5 of <em>EPB41L3</em> were the best HSIL predictors (AUC &gt;0.83) and CpG-site 4 for cancer (0.925). Combination of <em>EPB41L3</em> sites 2/4 plus <em>FAM19A4</em> site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity].</p><p>Methylation at CpG-site 5 of <em>FAM19A4</em> was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of <em>FAM19A4</em> for cancer (0.77). Combined, <em>FAM19A4</em> site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%.</p><p>In conclusion, methylation at individual CpG-sites of <em>EPB41L3</em> and <em>FAM19A4</em> outperformed global analysis and improved HSIL+ detection, warranting further investigation.</p></div>\",\"PeriodicalId\":52381,\"journal\":{\"name\":\"Tumour Virus Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2666679024000120/pdfft?md5=211b8be54b2e08277c81b68123f37b1d&pid=1-s2.0-S2666679024000120-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tumour Virus Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666679024000120\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"VIROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tumour Virus Research","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666679024000120","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"VIROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

基因启动子的全局甲基化分析有望用于检测高危人类乳头瘤病毒(hrHPV)阳性妇女的高级别或更严重的鳞状上皮内病变(HSIL+)。然而,单个 CpG 位点甲基化数据的诊断性能有限。我们对巴布亚新几内亚自采样本和临床医生采集样本中预测 HSIL+ 的甲基化情况进行了研究。通过对 44 份 HPV+样本(4 例癌症、19 例 HSIL、4 例低度鳞状上皮内病变 (LSIL)、17 例正常样本)进行热测序,评估了 EPB41L3(1-6 个 CpG 位点)、hTERT(1-10 个 CpG 位点)和 FAM19A4(1-5 个 CpG 位点)的甲基化情况。针对 FAM19A4 设计了新的引物,引物指向以前未探究过的第一个外显子区域。在临床医生采集的样本中,EPB41L3的CpG位点4和5的甲基化是预测HSIL的最佳指标(AUC>0.83),CpG位点4是预测癌症的最佳指标(0.925)。EPB41L3 2/4位点和FAM19A4 1位点的组合是最佳的HSIL+标记物[敏感性100%,特异性63.2%]。在自采样本中,FAM19A4 的 CpG 位点 5 的甲基化是预测 HSIL 的最佳指标(0.67),而 FAM19A4 的 CpG 位点 1 和 3 则是预测癌症的最佳指标(0.77)。结合 FAM19A4 位点 1 和 HPV 16/18 检测,灵敏度为 82.6%,特异性为 61.9%。总之,EPB41L3 和 FAM19A4 单个 CpG 位点的甲基化优于全局分析,提高了 HSIL+ 的检测率,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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 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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Tumour Virus Research
Tumour Virus Research Medicine-Infectious Diseases
CiteScore
6.50
自引率
2.30%
发文量
16
审稿时长
56 days
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信