Bi-directional crosstalk between the tumor and the tumor microenvironment (TME) has been shown to increase the rate of tumor evolution and to play a key role in neoplastic progression, therapeutic resistance, and a patient’s overall survival. Here, we set out to use a comprehensive liquid-biopsy analysis to study cancer and specific TME cells in circulation and their association with disease status. Cytokeratin+, CD45- circulating rare cells (CRCs) from nine breast and four prostate cancer patients were characterized through morphometrics, single-cell copy number analysis, and targeted multiplexed proteomics to delineate cancer cell lineage from other rare cells originating in the TME. We show that we can detect epithelial circulating tumor cells (EPI.CTC), CTCs undergoing epithelial-to-mesenchymal transition (EMT.CTC) and circulating endothelial cells (CECs) using a universal rare event detection platform (HDSCA). Longitudinal analysis of an index patient finds that CTCs are present at the time of disease progression, while CECs are predominately present at the time of stable disease. In a small cohort of prostate and breast cancer patients, we find high inter-patient and temporal intra-patient variability in the expression of tissue specific markers such as ER, HER2, AR, PSA and PSMA and EpCAM. Our study stresses the importance of the multi-omic characterization of circulating rare cells in patients with breast and prostate carcinomas, specifically highlighting overlapping and cell type defining proteo-genomic characteristics of CTCs and CECs.
肿瘤与肿瘤微环境（TME）之间的双向交互作用已被证实能够加速肿瘤演化速率，并在肿瘤进展、治疗抵抗以及患者总体生存率中发挥关键作用。本研究采用全面的液体活检分析技术，探究循环系统中的癌细胞及特定TME细胞，并阐释其与疾病状态的关联。通过对九例乳腺癌和四例前列腺癌患者来源的细胞角蛋白阳性、CD45阴性循环稀有细胞（CRCs）进行形态计量学、单细胞拷贝数分析和靶向多重蛋白质组学表征，我们成功区分了癌细胞系与源自TME的其他稀有细胞。研究证明，利用通用稀有事件检测平台（HDSCA）能够检测上皮性循环肿瘤细胞（EPI.CTC）、经历上皮-间质转化的循环肿瘤细胞（EMT.CTC）以及循环内皮细胞（CECs）。对一例典型患者的纵向分析发现，CTC在疾病进展期出现，而CEC主要存在于疾病稳定期。在前列腺癌和乳腺癌患者的小型队列中，我们观察到组织特异性标志物（如ER、HER2、AR、PSA、PSMA和EpCAM）的表达存在显著的个体间差异及个体内时间波动性。本研究强调了乳腺癌和前列腺癌患者循环稀有细胞多组学表征的重要性，特别揭示了CTC与CEC在蛋白质组-基因组特征上的重叠性与细胞类型界定性。
肿瘤(癌症)患者之家