Abstract:
Circulating tumor cells (CTCs) are noninvasive biomarkers that can indicate the therapeutic response and prognosis. The study aimed to investigate the cellular characteristics of CTCs focusing on monitoring during atezolizumab and bevacizumab (Atezo-Bev) therapy in patients with hepatocellular carcinoma (HCC). Peripheral blood samples were collected from 10 healthy controls and 40 patients with HCC. CTCs enriched using RosetteSep™ Human CD45 depletion cocktail were analyzed by multiparametric flow cytometry. CTC isolation was based on PanCK(+)CD45(-) cells, and CTCs exhibiting markers CD90, CD133, EpCAM, or vimentin. The total number of CTCs and the number of CTCs expressing CD90, CD133, EpCAM, and vimentin were correlated with the BCLC stage of HCC. The change in total CTC count accurately reflected the initial response to Atezo-Bev therapy. The numbers and mean fluorescence intensity of the CTC subsets expressing CD90 and EpCAM molecules decreased in patients with partial response/stable disease, and increased in patients with progressive disease and were markedly correlated with overall survival. CD90(+) and EpCAM(+) CTCs may be candidate biomarkers for the early prediction of the treatment response and the overall survival of patients with HCC receiving Atezo-Bev therapy.
摘要:
循环肿瘤细胞(CTC)是非侵入性生物标志物,其可以指示治疗应答和预后。该研究旨在研究CTC的细胞特征,重点是在atezolizumab和贝伐单抗(Atezo-Bev)治疗期间监测肝细胞癌(HCC)。从10名健康对照和40名HCC患者收集外周血样本。通过多参数流式细胞术分析使用RosetteSep™人类CD45消耗混合物富集的CTC。CTC分离基于PanCK(+)CD45(-)细胞,和CTC显示标志物CD90,CD133,EpCAM,或者波形蛋白.CTCs的总数和表达CD90、CD133、EpCAM、波形蛋白与HCC的BCLC分期相关。总CTC计数的变化准确地反映了对Atezo-Bev治疗的初始反应。部分缓解/疾病稳定的患者表达CD90和EpCAM分子的CTC亚群的数量和平均荧光强度降低,并且在进行性疾病患者中增加,并且与总生存率显着相关。CD90(+)和EpCAM(+)CTC可能是早期预测接受Atezo-Bev治疗的HCC患者的治疗反应和总体生存的候选生物标志物。