Division of Medical Oncology, Department of Medicine and Department of Biochemistry & Molecular Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Department of Population and Public Health Sciences, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Int J Mol Sci. 2022 Feb 25;23(5):2571. doi: 10.3390/ijms23052571.
Integrating liquid biopsies of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) with other minimally invasive measures may yield more comprehensive disease profiles. We evaluated the feasibility of concurrent cellular and molecular analysis of CTCs and cfDNA combined with radiomic analysis of CT scans from patients with metastatic castration-resistant PC (mCRPC). CTCs from 22 patients were enumerated, stained for PC-relevant markers, and clustered based on morphometric and immunofluorescent features using machine learning. DNA from single CTCs, matched cfDNA, and buffy coats was sequenced using a targeted amplicon cancer hotspot panel. Radiomic analysis was performed on bone metastases identified on CT scans from the same patients. CTCs were detected in 77% of patients and clustered reproducibly. cfDNA sequencing had high sensitivity (98.8%) for germline variants compared to WBC. Shared and unique somatic variants in PC-related genes were detected in cfDNA in 45% of patients (MAF > 0.1%) and in CTCs in 92% of patients (MAF > 10%). Radiomic analysis identified a signature that strongly correlated with CTC count and plasma cfDNA level. Integration of cellular, molecular, and radiomic data in a multi-parametric approach is feasible, yielding complementary profiles that may enable more comprehensive non-invasive disease modeling and prediction.
将循环肿瘤细胞（CTC）和游离细胞 DNA（cfDNA）的液体活检与其他微创措施相结合，可能会提供更全面的疾病概况。我们评估了对转移性去势抵抗性前列腺癌（mCRPC）患者的 CTC 和 cfDNA 的细胞和分子分析与 CT 扫描的放射组学分析同时进行的可行性。对 22 名患者的 CTC 进行计数，用针对 PC 的标记物对其进行染色，并使用机器学习根据形态和免疫荧光特征对其进行聚类。使用靶向扩增子癌症热点面板对单个 CTC 的 DNA、匹配的 cfDNA 和白细胞进行测序。对来自同一患者的 CT 扫描中发现的骨转移进行放射组学分析。77%的患者检测到 CTC，且可重复聚类。cfDNA 测序与白细胞相比，对种系变异具有更高的灵敏度（98.8%）。在 cfDNA 中，45%的患者（MAF>0.1%）和 92%的患者（MAF>10%）检测到 PC 相关基因中的共享和独特的体细胞变异。放射组学分析确定了一个与 CTC 计数和血浆 cfDNA 水平强烈相关的特征。在多参数方法中整合细胞、分子和放射组学数据是可行的，可产生互补的概况，从而可能实现更全面的非侵入性疾病建模和预测。
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