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首页> 美国卫生研究院文献>Cells >Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell Extracellular Vesicle and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients
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Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell Extracellular Vesicle and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients

机译：纵向多参数液体活组织检查方法识别循环肿瘤细胞细胞外囊泡和无细胞DNA表征的独特特征用于转移乳腺癌患者疾病监测

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Dynamics of mRNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) were assessed to examine the relevance of a longitudinal multi-parametric liquid biopsy strategy. Eighteen milliliters of blood was drawn from 27 hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients at disease progression and at two subsequent radiologic staging time points. CTC mRNA and EV mRNA were analyzed using multi-marker qPCR, and cfDNA was analyzed using targeted next-generation sequencing (NGS). The presence of ERBB2 or ERBB3 overexpression signals in CTCs significantly correlated with disease progression (87% specificity, 36% sensitivity, p-value = 0.023), and the presence of either ERBB3 signals in CTCs or EVs or cfDNA variants in ERBB3 also showed a significant association with progressive MBC. Fluctuations during treatment were detected in the EV fraction with the appearance of hitherto undetected ERCC1 signals correlating with progressive disease (97% specificity, 18% sensitivity, p-value = 0.030). Allele frequency development of ESR1 and PIK3CA variants detected at subsequent staging time points could be used as a predictor for therapy success and, importantly, might help guide therapy decisions. The three analytes, each with their own unique features for disease monitoring, were shown to be complementary, underlining the usefulness of the longitudinal multi-parametric liquid biopsy approach.
机译：评估来自细胞外囊泡（EVS）和无细胞DNA（CFDNA）的mRNA的动力学，以检查纵向多参数液体活检策略的相关性。从27个激素受体阳性和人表皮生长因子受体2（HER2）在疾病进展和两个后续放射学分期时间点中从27个激素受体阳性和人表皮生长因子受体2（MBC）患者中汲取了18毫升血液。使用多标记QPCR分析CTC mRNA和EV mRNA，使用靶向下一代测序（NGS）分析CFDNA。 CTC中的ERBB2或ERBB3过表达信号的存在显着与疾病进展（87％的特异性，36％敏感性，P值= 0.023）显着相关，以及ERBB3中的CTCS或EVS或CFDNA变体中的ERBB3信号的存在也显示出一个与渐进式MBC有关的关系。在EV部分中检测治疗期间的波动，迄今未知的ERCC1信号与渐进性疾病相关（97％特异性，18％敏感性，P值= 0.030）。在随后的分期时间点检测到的ESR1和PIK3CA变体的等位基因开发可以用作治疗成功的预测因子，并且重要的是，可能有助于指导治疗决策。三种分析物，每个分析物都具有自身的疾病监测特征，被证明是互补的，强调纵向多参数液体活检方法的有用性。

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