Papadaki Maria A, Mala Anastasia, Merodoulaki Aikaterini C, Vassilakopoulou Maria, Mavroudis Dimitrios, Agelaki Sofia
Laboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, Greece.
Department of Medical Oncology, University General Hospital of Heraklion, 71500 Heraklion, Greece.
Cancers (Basel). 2022 Aug 12;14(16):3903. doi: 10.3390/cancers14163903.
We herein aimed to assess the effect of eribulin mesylate on the cancer stem cell (CSC)/EMT-like phenotype of CTCs, and to investigate the prognostic role of CTC detection and monitoring for eribulin-treated BC patients. Peripheral blood was obtained at baseline ( = 42 patients) and 8 days after treatment initiation (C1D8: = 22), and on disease progression (PD: = 26). PBMCs cytospins were immunofluorescently stained for Cytokeratins/ALDH1/TWIST1/DAPI and analyzed via Ariol microscopy. CTCs were detected in 33.3%, 27.3%, and 23.1% of patients at baseline, C1D8, and PD, respectively. Accordingly, partial-EMT+ CTCs represented 61.3%, 0%, and 37.5% of total CTCs, whereas the CSC-like phenotype was consistently expressed by 87.5%, 75%, and 91.7% of CTCs at the respective time points. Interestingly, the CSC+/partial-EMT+ subset prevailed at baseline, but it was eradicated on C1D8 and resurged again during PD. CTC detection at baseline was associated with reduced PFS ( = 0.007) and OS ( = 0.005), and was an independent risk factor for death (HR: 3.779, = 0.001; multivariate analysis). The CSC+/partial-EMT+ CTCs emerged as the only subset with adverse prognostic significance, while CTC monitoring during eribulin therapy improved the prediction of disease progression. These results indicate that resistant CTC subsets persevere eribulin treatment and highlight the prognostic implications of CTC analyses for eribulin-treated BC patients.
我们旨在评估甲磺酸艾瑞布林对循环肿瘤细胞(CTC)的癌症干细胞(CSC)/上皮-间质转化(EMT)样表型的影响,并研究CTC检测和监测对接受艾瑞布林治疗的乳腺癌(BC)患者的预后作用。在基线期(n = 42例患者)、治疗开始后8天(C1D8:n = 22)和疾病进展期(PD:n = 26)采集外周血。对外周血单个核细胞(PBMC)涂片进行细胞角蛋白/醛脱氢酶1(ALDH1)/ Twist1/4',6-二脒基-2-苯基吲哚(DAPI)免疫荧光染色,并通过Ariol显微镜进行分析。在基线期、C1D8期和PD期分别有33.3%、27.3%和23.1%的患者检测到CTC。相应地,部分EMT + CTC分别占总CTC的61.3%、0%和37.5%,而在各个时间点,CSC样表型在CTC中持续表达的比例分别为87.5%、75%和91.7%。有趣的是,CSC + /部分EMT + 亚群在基线期占优势,但在C1D8期被清除,并在PD期再次出现。基线期CTC检测与无进展生存期(PFS,P = 0.007)和总生存期(OS,P = 0.005)缩短相关,并且是死亡的独立危险因素(风险比[HR]:3.779,P = 0.001;多变量分析)。CSC + /部分EMT + CTC是唯一具有不良预后意义的亚群,而在艾瑞布林治疗期间进行CTC监测可改善对疾病进展的预测。这些结果表明,耐药的CTC亚群在艾瑞布林治疗后持续存在,并突出了CTC分析对接受艾瑞布林治疗的BC患者的预后意义。