Colorectal cancer (CRC) colonoscopic surveillance is effective but burdensome. Circulating tumor DNA (ctDNA) analysis has emerged as a promising, minimally invasive tool for disease detection and management. Here, we assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood test. In this prospective, proof-of-concept study, patients with colonoscopies for Lynch surveillance or the National Colorectal Cancer screening program were included between 7 July 2019 and 3 June 2022. Blood was drawn, and if advanced neoplasia (adenoma with villous component, high-grade dysplasia, ≥10 mm, or CRC) was detected, it was analyzed for chromosomal copy number variations, single nucleotide variants, and genome-wide methylation (MeD-seq). Outcomes were compared with corresponding patients’ tissues and the MeD-seq results of healthy blood donors. Two Lynch carriers and eight screening program patients were included: five with CRC and five with advanced adenomas. cfDNA showed copy number variations and single nucleotide variants in one patient with CRC and liver metastases. Eight patients analyzed with MeD-seq showed clustering of Lynch-associated and sporadic microsatellite instable lesions separate from microsatellite stable lesions, as did healthy blood donors. In conclusion, whereas copy number changes and single nucleotide variants were only detected in one patient, cfDNA methylation profiles could discriminate all microsatellite instable advanced neoplasia, rendering this tool particularly promising for LS surveillance. Larger studies are warranted to validate these findings.
结直肠癌（CRC）结肠镜监测虽有效但负担较重。循环肿瘤DNA（ctDNA）分析已成为一种前景广阔、微创的疾病检测与管理工具。本研究旨在评估哪种ctDNA检测方法最适用于基于ctDNA的CRC筛查/监测血液检测。在这项前瞻性概念验证研究中，我们纳入了2019年7月7日至2022年6月3日期间因林奇综合征监测或国家结直肠癌筛查计划接受结肠镜检查的患者。采集血液样本后，若检出晚期肿瘤（含绒毛成分腺瘤、高级别上皮内瘤变、直径≥10毫米或CRC），则对其染色体拷贝数变异、单核苷酸变异及全基因组甲基化（MeD-seq）进行分析。检测结果与对应患者的组织样本及健康献血者的MeD-seq数据进行比较。研究共纳入2例林奇综合征携带者和8例筛查计划参与者：其中5例为CRC患者，5例为晚期腺瘤患者。循环游离DNA（cfDNA）仅在1例伴有肝转移的CRC患者中检测到拷贝数变异和单核苷酸变异。通过MeD-seq分析的8例患者显示，林奇综合征相关和散发性微卫星不稳定病变与微卫星稳定病变存在聚类分离，健康献血者亦呈现相同特征。结论表明，虽然仅1例患者检测到拷贝数改变和单核苷酸变异，但cfDNA甲基化谱可区分所有微卫星不稳定性晚期肿瘤，这使该技术在林奇综合征监测领域展现出独特潜力。后续需开展更大规模研究以验证这些发现。
肿瘤(癌症)患者之家