White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer
White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer
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DOI：
10.1038/s41467-020-14310-3
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发表时间：
2020-01-27
影响因子：
16.6
通讯作者：
Velculescu, Victor E.
中科院分区：
文献类型：
--
作者：
Leal, Alessandro;van Grieken, Nicole C. T.;Velculescu, Victor E.
液体活检为手术后检测无细胞DNA （cfDNA）中的残留疾病提供了新的机会，但可能会因克隆造血引起的改变而混淆。在这里，我们通过对来自同一患者的匹配cfDNA和白细胞的超灵敏靶向测序分析来鉴定循环肿瘤来源的DNA （ctDNA）改变。我们应用这种方法分析了批评家试验中患者的样本，这是一项针对可手术胃癌患者围手术期治疗的III期随机对照研究。在筛选匹配白细胞的改变后，在术前治疗和符合多模式治疗条件的患者手术后9周内分析ctDNA的存在预测复发。这些分析提供了一种区分ctDNA与其他cfDNA改变的简便方法，并强调了ctDNA作为胃癌患者围手术期癌症治疗和手术切除患者预后的预测性生物标志物的实用性。
Liquid biopsies are providing new opportunities for detection of residual disease in cell-free DNA (cfDNA) after surgery but may be confounded through identification of alterations arising from clonal hematopoiesis. Here, we identify circulating tumor-derived DNA (ctDNA) alterations through ultrasensitive targeted sequencing analyses of matched cfDNA and white blood cells from the same patient. We apply this approach to analyze samples from patients in the CRITICS trial, a phase III randomized controlled study of perioperative treatment in patients with operable gastric cancer. After filtering alterations from matched white blood cells, the presence of ctDNA predicts recurrence when analyzed within nine weeks after preoperative treatment and after surgery in patients eligible for multimodal treatment. These analyses provide a facile method for distinguishing ctDNA from other cfDNA alterations and highlight the utility of ctDNA as a predictive biomarker of patient outcome to perioperative cancer therapy and surgical resection in patients with gastric cancer.