检测结直肠癌患者血浆和尿液循环肿瘤 DNA 中的 KRAS 突变。
Detection of KRAS mutations in circulating tumour DNA from plasma and urine of patients with colorectal cancer.
机构信息
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan.
出版信息
Eur J Surg Oncol. 2021 Dec;47(12):3151-3156. doi: 10.1016/j.ejso.2021.07.017. Epub 2021 Jul 22.
BACKGROUND
Circulating tumour DNA (ctDNA) is very useful for purposes of cancer genetics; however, it has some limitations. Recently, ctDNA in body fluids, such as urine, sputum, and pleural effusion, has been investigated. The aim of this study was to evaluate the quantity of ctDNA derived from urine (trans-renal ctDNA) and the accuracy of KRAS mutation detection in relation to disease stage in colorectal cancer.
METHODS
Urine, plasma, and tissue samples were collected from consecutively resected colorectal cancer patients. DNA was extracted from each sample and the quantity was determined. From each DNA sample, KRAS mutations were detected using droplet digital PCR.
RESULTS
200 patients participated and KRAS mutations were detected in 84 patients (42.0%) from tumour tissue. The concentration of trans-renal ctDNA (trtDNA) was significantly lower than that of plasma; however, there was no significant difference between the sensitivity using ctDNA and that using trtDNA (29.8% VS 33.3%, p = 0.62). Concordance between these two tests was only 17.5%. Combination analysis (ctDNA + trtDNA) improved the sensitivity to 53.6%, and sensitivity was significantly higher than that of corresponding single assays (p = 0.003). In early cancer stages, trtDNA had greater sensitivity for detecting KRAS mutations than ctDNA (37.7% vs. 21.3%, p = 0.047). Conversely, it was less useful for advanced cancer stages (21.7% vs. 52.2%, p = 0.07). Notably, KRAS mutations were detected using ctDNA or trtDNA in 12 of 116 (10.3%) patients who had no KRAS mutations in their tissue samples.
CONCLUSIONS
trtDNA and ctDNA have equal potential and combination analysis significantly improved the sensitivity.
背景
循环肿瘤 DNA（ctDNA）在癌症遗传学方面非常有用；然而，它有一些局限性。最近，人们研究了体液（如尿液、痰和胸腔积液）中的 ctDNA。本研究旨在评估源自尿液的 ctDNA 量（跨肾 ctDNA）以及在结直肠癌中与疾病分期相关的 KRAS 突变检测的准确性。
方法
连续收集接受切除术的结直肠癌患者的尿液、血浆和组织样本。从每个样本中提取 DNA 并确定其数量。从每个 DNA 样本中，使用液滴数字 PCR 检测 KRAS 突变。
结果
200 名患者参与，84 名（42.0%）肿瘤组织患者检测到 KRAS 突变。跨肾 ctDNA（trtDNA）的浓度明显低于血浆；然而，ctDNA 和 trtDNA 的敏感性之间没有显著差异（29.8%比 33.3%，p=0.62）。这两种检测的一致性仅为 17.5%。联合分析（ctDNA+trtDNA）将敏感性提高至 53.6%，敏感性明显高于相应的单项检测（p=0.003）。在早期癌症阶段，trtDNA 检测 KRAS 突变的敏感性高于 ctDNA（37.7%比 21.3%，p=0.047）。相反，它对晚期癌症阶段的作用较小（21.7%比 52.2%，p=0.07）。值得注意的是，在 116 名组织样本中无 KRAS 突变的患者中，有 12 名（10.3%）使用 ctDNA 或 trtDNA 检测到 KRAS 突变。
结论
trtDNA 和 ctDNA 具有同等潜力，联合分析显著提高了敏感性。
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