Centre for Cardiothoracic Surgery, Xiangyang Central Hospital, Hospital Affiliated to Hubei University of Arts and Science, Xiangyang 441021, Hubei, China.
General Thoracic Surgery, Yicheng People's Hospital, Xiangyang 441400, Hubei, China.
Cancer Biomark. 2018;23(3):427-436. doi: 10.3233/CBM-181511.
The need for less invasive procedures for lung cancer probing is critically needed to better understand the disease. The purpose of the current study aims to explore the use of circulating tumor DNA (ctDNA) derived from plasma and urine specimens.
Matched peripheral blood and morning urine specimens were obtained from 160 late stage NSCLC patients. The amount of ctDNA was quantified for each of the patients. Activating and sensitizing EGFR mutations commonly found in NSCLC patients were profiled. Longitudinal analysis was performed to compared DNA variations during disease progression.
Measurement of EGFR mutations in NSCLC patients using plasma and urinal DNA demonstrated strong concordance to conventional tissue biopsy profiling. Baseline matched tumor samples yielded 82.8% and 84.0% for plasma and urinal DNA respectively. For these measurements, the positive predictive value was 100% for plasma and urinal DNA. In the longitudinal study, we observed strong links to disease severity and survival analysis showed a clear trend with patients having higher DNA concentrations to have worse outcome especially for urinal DNA. HR for patients stratified using plasma and urinal DNA were 1.23 and 2.55 respectively.
Measurements of circulating DNA within body fluids presented potentially new tools for the disease management of NSCLC patients with EGFR mutations. We demonstrated both plasma and urinal DNA correlated well to tissue biopsies and were potentially prognostic to address patients' survival outcome.
迫切需要对肺癌进行侵入性较小的探测程序，以便更好地了解这种疾病。本研究旨在探索使用源自血浆和尿液标本的循环肿瘤 DNA（ctDNA）。
从 160 名晚期 NSCLC 患者中采集了配对的外周血和晨尿标本。对每位患者的 ctDNA 量进行了定量分析。对常见于 NSCLC 患者的激活和致敏 EGFR 突变进行了分析。进行了纵向分析，以比较疾病进展过程中的 DNA 变化。
使用血浆和尿 DNA 对 NSCLC 患者进行 EGFR 突变的测量与常规组织活检分析具有很强的一致性。基线匹配的肿瘤样本分别产生了 82.8%和 84.0%的血浆和尿 DNA。对于这些测量，血浆和尿 DNA 的阳性预测值均为 100%。在纵向研究中，我们观察到与疾病严重程度之间存在很强的联系，生存分析显示出明显的趋势，即 DNA 浓度较高的患者预后较差，尤其是尿 DNA。使用血浆和尿 DNA 分层的患者的 HR 分别为 1.23 和 2.55。
体液中循环 DNA 的测量为 EGFR 突变的 NSCLC 患者的疾病管理提供了潜在的新工具。我们证明了血浆和尿 DNA 与组织活检均具有良好的相关性，并且对预测患者的生存结局具有潜在的预后价值。
