A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2024-12-01 Epub Date: 2024-07-14 DOI:10.1080/15592294.2024.2374988
Chunxiao Bu, Zhilong Wang, Xianping Lv, Yanteng Zhao
{"title":"A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection.","authors":"Chunxiao Bu, Zhilong Wang, Xianping Lv, Yanteng Zhao","doi":"10.1080/15592294.2024.2374988","DOIUrl":null,"url":null,"abstract":"<p><p>Early detection is crucial for increasing the survival rate of gastric cancer (GC). We aimed to identify a methylated cell-free DNA (cfDNA) marker panel for detecting GC. The differentially methylated CpGs (DMCs) were selected from datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The selected DMCs were validated and further selected in tissue samples (40 gastric cancer and 36 healthy white blood cell samples) and in a quarter sample volume of plasma samples (37 gastric cancer, 12 benign gastric disease, and 43 healthy individuals). The marker combination selected was then evaluated in a normal sample volume of plasma samples (35 gastric cancer, 39 control diseases, and 40 healthy individuals) using real-time methylation-specific PCR (MSP). The analysis of the results compared methods based on 2<sup>-ΔΔCt</sup> values and Ct values. In the results, 30 DMCs were selected through bioinformatics methods, and then 5 were selected for biological validation. The marker combination of two fragments of IRF4 (IRF4-1 and IRF4-2) and one of ZEB2 was selected due to its good performance. The Ct-based method was selected for its good results and practical advantages. The assay, IRF4-1 and IRF4-2 in one fluorescence channel and ZEB2 in another, obtained 74.3% sensitivity for the GC group at any stage, at 92.4% specificity. In conclusion, the panel of IRF4 and ZEB2 in plasma cfDNA demonstrates good diagnostic performance and application potential in clinical settings.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2374988"},"PeriodicalIF":2.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249030/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15592294.2024.2374988","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/14 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Early detection is crucial for increasing the survival rate of gastric cancer (GC). We aimed to identify a methylated cell-free DNA (cfDNA) marker panel for detecting GC. The differentially methylated CpGs (DMCs) were selected from datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The selected DMCs were validated and further selected in tissue samples (40 gastric cancer and 36 healthy white blood cell samples) and in a quarter sample volume of plasma samples (37 gastric cancer, 12 benign gastric disease, and 43 healthy individuals). The marker combination selected was then evaluated in a normal sample volume of plasma samples (35 gastric cancer, 39 control diseases, and 40 healthy individuals) using real-time methylation-specific PCR (MSP). The analysis of the results compared methods based on 2-ΔΔCt values and Ct values. In the results, 30 DMCs were selected through bioinformatics methods, and then 5 were selected for biological validation. The marker combination of two fragments of IRF4 (IRF4-1 and IRF4-2) and one of ZEB2 was selected due to its good performance. The Ct-based method was selected for its good results and practical advantages. The assay, IRF4-1 and IRF4-2 in one fluorescence channel and ZEB2 in another, obtained 74.3% sensitivity for the GC group at any stage, at 92.4% specificity. In conclusion, the panel of IRF4 and ZEB2 in plasma cfDNA demonstrates good diagnostic performance and application potential in clinical settings.

用于胃癌检测的血浆无细胞 DNA 中两个甲基化 IRF4 片段和一个 ZEB2 片段的双基因面板。
早期检测对于提高胃癌(GC)的存活率至关重要。我们的目标是确定一个用于检测胃癌的甲基化无细胞DNA(cfDNA)标记物面板。我们从癌症基因组图谱(The Cancer Genome Atlas,TCGA)和基因表达总库(Gene Expression Omnibus,GEO)数据库中筛选出了差异甲基化CpGs(DMCs)。选定的 DMCs 在组织样本(40 份胃癌样本和 36 份健康白细胞样本)和四分之一样本量的血浆样本(37 份胃癌样本、12 份良性胃病样本和 43 份健康人血浆样本)中得到验证和进一步筛选。然后使用实时甲基化特异性 PCR(MSP)在正常血浆样本量(35 例胃癌、39 例对照疾病和 40 例健康人)中对所选标记物组合进行评估。结果分析比较了基于 2-ΔΔCt 值和 Ct 值的方法。结果显示,通过生物信息学方法筛选出了 30 个 DMCs,然后选择了 5 个进行生物学验证。由两个 IRF4 片段(IRF4-1 和 IRF4-2)和一个 ZEB2 片段组成的标记组合因其性能良好而被选中。基于 Ct 的方法因其良好的结果和实用性而被选中。该检测方法在一个荧光通道中检测 IRF4-1 和 IRF4-2,在另一个荧光通道中检测 ZEB2,对任何阶段的 GC 组的敏感性为 74.3%,特异性为 92.4%。总之,血浆 cfDNA 中的 IRF4 和 ZEB2 面板显示出良好的诊断性能和临床应用潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Epigenetics
Epigenetics 生物-生化与分子生物学
CiteScore
6.80
自引率
2.70%
发文量
82
审稿时长
3-8 weeks
期刊介绍: Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed. Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to): DNA methylation Nucleosome positioning and modification Gene silencing Imprinting Nuclear reprogramming Chromatin remodeling Non-coding RNA Non-histone chromosomal elements Dosage compensation Nuclear organization Epigenetic therapy and diagnostics Nutrition and environmental epigenetics Cancer epigenetics Neuroepigenetics
×
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