血浆中循环肿瘤 DNA 的检测：食管腺癌的一种潜在生物标志物。
Detection of Circulating Tumor DNA in Plasma: A Potential Biomarker for Esophageal Adenocarcinoma.
机构信息
Department of Surgery, Boston University/Boston Medical Center, Boston, Massachusetts.
Department of Medicine, University of Rochester, Rochester, New York.
出版信息
Ann Thorac Surg. 2019 Aug;108(2):343-349. doi: 10.1016/j.athoracsur.2019.04.004. Epub 2019 May 3.
BACKGROUND
Recent literature has demonstrated the potential of "liquid biopsy" and detection of circulating tumor (ct)DNA as a cancer biomarker. However, to date there is a lack of data specific to esophageal adenocarcinoma (EAC). This study was conducted to determine how detection and quantification of ctDNA changes with disease burden in patients with EAC and evaluate its potential as a biomarker in this population.
METHODS
Blood samples were obtained from patients with stage I to IV EAC. Longitudinal blood samples were collected from a subset of patients. Imaging studies and pathology reports were reviewed to determine disease course. Tumor samples were sequenced to identify mutations. Mutations in plasma DNA were detected using custom, barcoded, patient-specific sequencing libraries. Mutations in plasma were quantified, and associations with disease stage and response to therapy were explored.
RESULTS
Plasma samples from a final cohort of 38 patients were evaluated. Baseline plasma samples were ctDNA positive for 18 patients (47%) overall, with tumor allele frequencies ranging from 0.05% to 5.30%. Detection frequency of ctDNA and quantity of ctDNA increased with stage. Data from longitudinal samples indicate that ctDNA levels correlate with and precede evidence of response to therapy or recurrence.
CONCLUSIONS
ctDNA can be detected in plasma of EAC patients and correlates with disease burden. Detection of ctDNA in early-stage EAC is challenging and may limit diagnostic applications. However, our data demonstrate the potential of ctDNA as a dynamic biomarker to monitor treatment response and disease recurrence in patients with EAC.
背景
近期文献表明，“液体活检”和循环肿瘤（ct）DNA 检测作为癌症生物标志物具有一定的潜力。然而，目前针对食管腺癌（EAC）的相关数据仍较为缺乏。本研究旨在确定 ctDNA 在 EAC 患者中的疾病负担变化及其检测和定量情况，并评估其在该人群中的潜在应用价值。
方法
采集 I 期至 IV 期 EAC 患者的血液样本。采集部分患者的纵向血液样本。通过影像学研究和病理报告来确定疾病进程。对肿瘤样本进行测序以识别突变。使用定制的、带条码的、患者特异性测序文库来检测血浆 DNA 中的突变。对血浆中的突变进行定量，并探讨其与疾病分期和治疗反应的相关性。
结果
对最终队列中的 38 名患者的血浆样本进行了评估。38 名患者的基线血浆样本中，有 18 名（47%）患者的 ctDNA 呈阳性，肿瘤等位基因频率范围为 0.05%至 5.30%。ctDNA 的检测频率和 ctDNA 的数量随疾病分期而增加。纵向样本数据表明，ctDNA 水平与治疗反应或复发的证据相关且先于其出现。
结论
ctDNA 可在 EAC 患者的血浆中检测到，并与疾病负担相关。在早期 EAC 中检测 ctDNA 具有一定挑战性，可能限制其诊断应用。然而，我们的数据表明 ctDNA 作为一种动态生物标志物，具有监测 EAC 患者治疗反应和疾病复发的潜力。
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