Plasma methylated GNB4 and Riplet as a novel dual-marker panel for the detection of hepatocellular carcinoma.

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Epigenetics Pub Date : 2024-12-01 Epub Date: 2023-12-28 DOI:10.1080/15592294.2023.2299044
Yanteng Zhao, Lei Zhao, Huifang Jin, Ying Xie, Liyinghui Chen, Wei Zhang, Lanlan Dong, Lianglu Zhang, Yue Huang, Kangkang Wan, Qiankun Yang, Shaochi Wang
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引用次数: 0

Abstract

Early detection of hepatocellular carcinoma (HCC) can greatly improve the survival rate of patients. We aimed to develop a novel marker panel based on cell-free DNA (cfDNA) methylation for the detection of HCC. The differentially methylated CpG sites (DMCs) specific for HCC blood diagnosis were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then validated by the whole genome bisulphite sequencing (WGBS) of 12 paired HCC and paracancerous tissues. The clinical performance of the panel was evaluated using tissue samples [32 HCC, chronic liver disease (CLD), and healthy individuals] and plasma cohorts (173 HCC, 199 CLD, and 98 healthy individuals). The combination of G protein subunit beta 4 (GNB4) and Riplet had the optimal area under the curve (AUC) in seven candidates through TCGA, GEO, and WGBS analyses. In tissue validation, the GNB4 and Riplet showed an AUC of 100% with a sensitivity and specificity of 100% for detecting any-stage HCC. In plasma, it demonstrated a high sensitivity of 84.39% at 91.92% specificity, with an AUC of 92.51% for detecting any-stage HCC. The dual-marker panel had a higher sensitivity of 78.26% for stage I HCC than alpha-fetoprotein (AFP) of 47.83%, and a high sensitivity of 70.27% for detecting a single tumour (size ≤3 cm). In conclusion, we developed a novel dual-marker panel that demonstrates high accuracy in detecting HCC, surpassing the performance of AFP testing.

血浆甲基化 GNB4 和 Riplet 作为检测肝细胞癌的新型双标记物面板。
早期发现肝细胞癌(HCC)可大大提高患者的生存率。我们旨在开发一种基于无细胞DNA(cfDNA)甲基化的新型标记物面板,用于检测HCC。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)数据库中筛选出了血液诊断 HCC 的特异性差异甲基化 CpG 位点(DMCs),然后对 12 个配对的 HCC 和癌旁组织进行了全基因组亚硫酸氢盐测序(WGBS)验证。利用组织样本(32 例 HCC、慢性肝病(CLD)和健康人)和血浆队列(173 例 HCC、199 例慢性肝病和 98 例健康人)对面板的临床性能进行了评估。通过TCGA、GEO和WGBS分析,G蛋白亚基β4(GNB4)和Riplet的组合在七个候选样本中具有最佳的曲线下面积(AUC)。在组织验证中,GNB4 和 Riplet 的 AUC 为 100%,对检测任何阶段的 HCC 的灵敏度和特异性均为 100%。在血浆中,检测任何阶段的 HCC 的灵敏度为 84.39%,特异性为 91.92%,AUC 为 92.51%。与甲胎蛋白(AFP)47.83%的灵敏度相比,双标记物检测 I 期 HCC 的灵敏度更高(78.26%),检测单个肿瘤(大小≤3 厘米)的灵敏度也高达 70.27%。总之,我们开发的新型双标记物面板在检测 HCC 方面具有很高的准确性,其性能超过了甲胎蛋白检测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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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
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