Multiparametric liquid biopsy analysis in metastatic prostate cancer
Multiparametric liquid biopsy analysis in metastatic prostate cancer
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DOI：
10.1172/jci.insight.125529
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发表时间：
2019-03-07
期刊：
影响因子：
8
通讯作者：
Goldkorn, Amir
中科院分区：
文献类型：
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作者：
Hodara, Emmanuelle;Morrison, Gareth;Goldkorn, Amir
用液体活检（例如循环肿瘤细胞（CTC））和无细胞核酸分析）对前列腺癌进行分子分析，产生信息丰富但独特的数据集。可以通过同时询问多个液体活检组分来获得额外的见解，以构建更全面的分子疾病谱。我们进行了一项初步的原理验证研究，旨在试点这种多参数方法。同时分析转移性去势抵抗性前列腺癌男性外周血样本的CTC计数、单细胞拷贝数变异、CTC DNA和匹配的游离DNA突变以及雄激素受体（AR）和AR剪接变体（ARV7）的血浆游离RNA水平。此外，将液体活检与匹配的肿瘤特征进行比较（如果可用），并在疾病进展时在一个患者亚组中进行第二次液体活检并进行分析。以这种方式，成功地为每个患者和时间点生成了多参数液体活检谱，证明了这种方法的可行性，并突出了共享以及独特的癌症相关变化。随着在大型队列中的进一步完善和验证，多参数液体活检可以最佳地整合不同但临床信息丰富的数据集，并最大限度地提高其在分子导向的实时患者管理中的效用。
Molecular profiling of prostate cancer with liquid biopsies, such as circulating tumor cells (CTCs) and cell-free nucleic acid analysis, yields informative yet distinct data sets. Additional insights may be gained by simultaneously interrogating multiple liquid biopsy components to construct a more comprehensive molecular disease profile. We conducted an initial proof-of-principle study aimed at piloting this multiparametric approach. Peripheral blood samples from men with metastatic castrate-resistant prostate cancer were analyzed simultaneously for CTC enumeration, single-cell copy number variations, CTC DNA and matched cell-free DNA mutations, and plasma cell-free RNA levels of androgen receptor (AR) and AR splice variant (ARV7). In addition, liquid biopsies were compared with matched tumor profiles when available, and a second liquid biopsy was drawn and analyzed at disease progression in a subset of patients. In this manner, multiparametric liquid biopsy profiles were successfully generated for each patient and time point, demonstrating the feasibility of this approach and highlighting shared as well as unique cancer-relevant alterations. With further refinement and validation in large cohorts, multiparametric liquid biopsies can optimally integrate disparate but clinically informative data sets and maximize their utility for molecularly directed, real-time patient management.