对结直肠癌、腺瘤和正常组织的表观基因组全甲基化分析揭示了解决未满足临床需求的新型生物标记物。

IF 5.7 2区 医学 Q1 Medicine
Katleen Janssens, Isabelle Neefs, Joe Ibrahim, Anne Schepers, Patrick Pauwels, Marc Peeters, Guy Van Camp, Ken Op de Beeck
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引用次数: 0

摘要

背景:大肠癌生物标志物的发现主要集中于正常组织和大肠肿瘤组织的甲基化模式,但腺瘤的研究仍然不足。因此,我们进行了首次表观基因组范围的研究,对所有三种组织类型的甲基化进行了综合分析,并确定了具有鉴别性的生物标志物:我们共收集了 1 892 份结直肠样本的公开甲基化阵列数据(Illumina EPIC 和 450K)。对两种阵列类型的组织类型进行配对差异甲基化分析,以 "双证 "差异甲基化探针(DE DMPs)。随后,根据甲基化水平筛选出差异甲基化探针,并利用它们建立二元逻辑回归预测模型。以临床上最有趣的组别(腺瘤与癌)为重点,我们发现了 13 个 DE DMPs,它们能有效区分腺瘤与癌(AUC = 0.996)。我们在一个包含 13 个腺瘤和 9 个癌的内部实验甲基化数据集中验证了这一模型。其灵敏度和特异度分别达到 96% 和 95%,总体准确率为 96%。我们的研究结果表明,本研究中发现的 13 个 DE DMPs 有可能在临床中用作分子生物标记物:我们的分析表明,甲基化生物标志物具有区分结直肠正常组织、前体组织和癌组织的潜力。更重要的是,我们强调了甲基化组作为区分结直肠腺瘤和癌的标记物来源的能力,而这一问题目前仍未得到满足。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Epigenome-wide methylation analysis of colorectal carcinoma, adenoma and normal tissue reveals novel biomarkers addressing unmet clinical needs.

Epigenome-wide methylation analysis of colorectal carcinoma, adenoma and normal tissue reveals novel biomarkers addressing unmet clinical needs.

Epigenome-wide methylation analysis of colorectal carcinoma, adenoma and normal tissue reveals novel biomarkers addressing unmet clinical needs.

Epigenome-wide methylation analysis of colorectal carcinoma, adenoma and normal tissue reveals novel biomarkers addressing unmet clinical needs.

Background: Biomarker discovery in colorectal cancer has mostly focused on methylation patterns in normal and colorectal tumor tissue, but adenomas remain understudied. Therefore, we performed the first epigenome-wide study to profile methylation of all three tissue types combined and to identify discriminatory biomarkers.

Results: Public methylation array data (Illumina EPIC and 450K) were collected from a total of 1 892 colorectal samples. Pairwise differential methylation analyses between tissue types were performed for both array types to "double evidence" differentially methylated probes (DE DMPs). Subsequently, the identified DMPs were filtered on methylation level and used to build a binary logistic regression prediction model. Focusing on the clinically most interesting group (adenoma vs carcinoma), we identified 13 DE DMPs that could effectively discriminate between them (AUC = 0.996). We validated this model in an in-house experimental methylation dataset of 13 adenomas and 9 carcinomas. It reached a sensitivity and specificity of 96% and 95%, respectively, with an overall accuracy of 96%. Our findings raise the possibility that the 13 DE DMPs identified in this study can be used as molecular biomarkers in the clinic.

Conclusions: Our analyses show that methylation biomarkers have the potential to discriminate between normal, precursor and carcinoma tissues of the colorectum. More importantly, we highlight the power of the methylome as a source of markers for discriminating between colorectal adenomas and carcinomas, which currently remains an unmet clinical need.

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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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