Institute of Molecular Cancer Research, University of Zurich, Zurich, Switzerland.
Department of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland.
BMC Cancer. 2023 Oct 18;23(1):998. doi: 10.1186/s12885-023-11487-w.
We previously identified 16,772 colorectal cancer-associated hypermethylated DNA regions that were also detectable in precancerous colorectal lesions (preCRCs) and unrelated to normal mucosal aging. We have now conducted a study to validate 990 of these differentially methylated DNA regions (DMRs) in a new series of preCRCs.
We used targeted bisulfite sequencing to validate these 990 potential biomarkers in 59 preCRC tissue samples (41 conventional adenomas, 18 sessile serrated lesions), each with a patient-matched normal mucosal sample. Based on differential DNA methylation tests, a panel of candidate DMRs was chosen on a subset of our cohort and then validated on the remaining part of our cohort and two publicly available datasets with respect to their stratifying potential between preCRCs and normal mucosa.
Strong statistical significance for the difference in methylation levels was observed across the full set of 990 investigated DMRs. From these, a selected candidate panel of 30 DMRs correctly identified 58/59 tumors (area under the receiver operating curve: 0.998).
These validated DNA hypermethylation markers can be exploited to develop more accurate noninvasive colorectal tumor screening assays.
我们先前鉴定了 16772 个与结直肠癌相关的超甲基化 DNA 区域，这些区域在癌前结直肠病变（preCRC）中也可检测到，且与正常黏膜衰老无关。我们现在进行了一项研究，在新的 preCRC 系列中验证了其中 990 个差异甲基化 DNA 区域（DMR）。
我们使用靶向亚硫酸氢盐测序来验证 59 个 preCRC 组织样本（41 个传统腺瘤，18 个无蒂锯齿状病变）中这 990 个潜在生物标志物中的 990 个，每个样本均有患者匹配的正常黏膜样本。基于差异 DNA 甲基化测试，在我们的队列中的一部分选择了一组候选 DMR 进行验证，然后在我们队列的其余部分和两个公开的数据集上验证了这些候选 DMR，以评估它们在 preCRC 和正常黏膜之间的分层潜力。
在 990 个研究的 DMR 中，观察到了全组甲基化水平差异的强烈统计学意义。其中，一组 30 个候选 DMR 可以正确识别 58/59 个肿瘤（接收者操作特征曲线下面积：0.998）。
这些经验证的 DNA 过度甲基化标志物可用于开发更准确的非侵入性结直肠肿瘤筛查检测。
