Serum DNA methylome of the colorectal cancer serrated pathway enables non-invasive detection.

IF 6.6 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Molecular Oncology Pub Date : 2024-11-01 Epub Date: 2024-01-10 DOI:10.1002/1878-0261.13573
María Gallardo-Gómez, Lara Costas-Ríos, Carlos A Garcia-Prieto, Lara Álvarez-Rodríguez, Luis Bujanda, Maialen Barrero, Antoni Castells, Francesc Balaguer, Rodrigo Jover, Manel Esteller, Antoni Tardío Baiges, Joaquín González-Carreró Fojón, Joaquín Cubiella, Loretta De Chiara
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Abstract

The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell-free DNA (cfDNA) methylomes as a potential source of biomarkers for the non-invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high-risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway-specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate-rich 1 (ERICH1) methylation discriminated high-risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non-invasive detection of colorectal serrated lesions.

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大肠癌锯齿状通路的血清 DNA 甲基组实现了无创检测。
结直肠癌锯齿状通路的临床相关性显而易见,但筛查锯齿状病变仍具有挑战性。我们的目的是描述锯齿状通路的血清甲基组特征,并评估循环无细胞DNA(cfDNA)甲基组作为无创检测锯齿状病变的潜在生物标志物来源。我们收集了锯齿状腺癌(SAC)患者、传统锯齿状腺瘤患者、无柄锯齿状病变患者、增生性息肉患者和无结直肠病变患者的血清样本。首先,我们用 MethylationEPIC 阵列量化了 cfDNA 甲基化。然后,我们将甲基化图谱与组织和血清数据集进行了比较。最后,我们评估了血清 cfDNA 甲基化生物标志物的效用。我们发现了一种能够区分高危锯齿状病变和无锯齿状肿瘤的差异甲基化图谱,它与来自 SAC 和无柄锯齿状病变的组织甲基化一致。血清甲基化图谱具有通路特异性,能明确区分锯齿状病变和传统腺瘤。宁久林2(NINJ2)和富谷氨酸1(ERICH1)甲基化的组合以91.4%的灵敏度(64.4%的特异性)区分高风险锯齿状病变和SAC,而锌指蛋白718(ZNF718)甲基化对检测SAC的灵敏度为100%(特异性为96%)。这是首个探索锯齿状病变血清甲基组的研究。cfDNA 的差异甲基化可用于无创检测结直肠锯齿状病变。
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来源期刊
Molecular Oncology
Molecular Oncology Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
11.80
自引率
1.50%
发文量
203
审稿时长
10 weeks
期刊介绍: Molecular Oncology highlights new discoveries, approaches, and technical developments, in basic, clinical and discovery-driven translational cancer research. It publishes research articles, reviews (by invitation only), and timely science policy articles. The journal is now fully Open Access with all articles published over the past 10 years freely available.
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