Division of Surgical Oncology, Department of Surgery and University of Southern California Norris Cancer Center, University of Southern California, Los Angeles, CA, USA.
Department of Hematology and Medical Oncology, University Hospital Zurich, Zurich, Switzerland.
Ann Surg Oncol. 2022 May;29(5):2882-2894. doi: 10.1245/s10434-021-11135-2. Epub 2022 Jan 9.
Metastatic breast cancer (MBC) and the circulating tumor cells (CTCs) leading to macrometastases are inherently different than primary breast cancer. We evaluated whether whole transcriptome RNA-Seq of CTCs isolated via an epitope-independent approach may serve as a surrogate for biopsies of macrometastases.
We performed RNA-Seq on fresh metastatic tumor biopsies, CTCs, and peripheral blood (PB) from 19 newly diagnosed MBC patients. CTCs were harvested using the ANGLE Parsortix microfluidics system to isolate cells based on size and deformability, independent of a priori knowledge of cell surface marker expression.
Gene expression separated CTCs, metastatic biopsies, and PB into distinct groups despite heterogeneity between patients and sample types. CTCs showed higher expression of immune oncology targets compared with corresponding metastases and PB. Predictive biomarker (n = 64) expression was highly concordant for CTCs and metastases. Repeat observation data post-treatment demonstrated changes in the activation of different biological pathways. Somatic single nucleotide variant analysis showed increasing mutational complexity over time.
We demonstrate that RNA-Seq of CTCs could serve as a surrogate biomarker for breast cancer macrometastasis and yield clinically relevant insights into disease biology and clinically actionable targets.
转移性乳腺癌（MBC）和导致巨转移的循环肿瘤细胞（CTC）与原发性乳腺癌本质上不同。我们评估了通过非表型依赖方法分离的 CTC 的全转录组 RNA-Seq 是否可以作为巨转移活检的替代物。
我们对 19 名新诊断的 MBC 患者的新鲜转移性肿瘤活检、CTC 和外周血（PB）进行了 RNA-Seq。CTC 使用 ANGLE Parsortix 微流控系统收获，该系统基于大小和变形性分离细胞，而不依赖于细胞表面标志物表达的先验知识。
尽管患者和样本类型之间存在异质性，但基因表达将 CTC、转移性活检和 PB 分成了不同的组。与相应的转移和 PB 相比，CTC 表现出更高的免疫肿瘤学靶标表达。预测生物标志物（n=64）在 CTC 和转移中的表达高度一致。治疗后重复观察数据显示不同生物学途径的激活发生了变化。体细胞单核苷酸变异分析显示随着时间的推移突变复杂性增加。
我们证明了 CTC 的 RNA-Seq 可以作为乳腺癌巨转移的替代生物标志物，并为疾病生物学和临床可操作的靶点提供有临床意义的见解。
