Frydendahl Amanda, Widman Adam J, Øgaard Nadia, Arora Anushri, Halmos Daniel, Nors Jesper, Ahrenfeldt Johanne, Henriksen Tenna V, Demuth Christina, Raaby Line, Rasmussen Mads H, Therkildsen Christina, Landau Dan A, Andersen Claus L
Department of Molecular Medicine, Aarhus University Hospital, Denmark.
Department of Clinical Medicine, Aarhus University, Denmark.
Mol Oncol. 2025 Apr;19(4):984-993. doi: 10.1002/1878-0261.13803. Epub 2025 Jan 20.
The presence of circulating tumor DNA (ctDNA) in patients with colorectal adenomas remains uncertain. Studies using tumor-agnostic approaches report ctDNA in 10-15% of patients, though with uncertainty as to whether the signal originates from the adenoma. To obtain an accurate estimate of the proportion of patients with ctDNA, a sensitive tumor-informed strategy is preferred, as it ensures the detected signal originates from the adenoma. Here, tumor-informed whole-genome sequencing-based ctDNA analysis (MRD-EDGE) was applied to two independent cohorts. Cohort 1, comprising 93 patients with stage III colorectal cancer (CRC) and 40 healthy individuals, was used to establish the signal threshold at 95% specificity. This threshold was then applied to Cohort 2, consisting of 22 patients with symptomatic and 20 with asymptomatic adenomas. In stage III, MRD-EDGE had an area under the curve of 0.98. ctDNA was detected in 50% and 25% of patients with symptomatic and asymptomatic adenomas, respectively. The median adenoma plasma tumor fraction was 5.9 × 10. These finding not only demonstrate the feasibility of ctDNA detection in patients with colorectal adenomas, but also provides an estimate of the necessary sensitivity required to detect these lesions, paving the way for future ctDNA-based screening strategies.
结直肠腺瘤患者循环肿瘤DNA（ctDNA）的存在情况仍不确定。采用非肿瘤特异性方法的研究报告称，10%-15%的患者存在ctDNA，不过对于该信号是否源自腺瘤尚不确定。为了准确估计ctDNA阳性患者的比例，采用基于肿瘤信息的敏感策略更为可取，因为它能确保检测到的信号源自腺瘤。在此，基于肿瘤信息的全基因组测序ctDNA分析（MRD-EDGE）应用于两个独立队列。队列1包括93例III期结直肠癌（CRC）患者和40名健康个体，用于在95%特异性水平确定信号阈值。然后将该阈值应用于队列2，队列2由22例有症状腺瘤患者和20例无症状腺瘤患者组成。在III期，MRD-EDGE的曲线下面积为0.98。有症状和无症状腺瘤患者中ctDNA的检测率分别为50%和25%。腺瘤血浆肿瘤分数中位数为5.9×10。这些发现不仅证明了在结直肠腺瘤患者中检测ctDNA的可行性，还提供了检测这些病变所需的必要灵敏度的估计值，为未来基于ctDNA的筛查策略铺平了道路。
