Miklikova Svetlana, Minarik Gabriel, Sedlackova Tatiana, Plava Jana, Cihova Marina, Jurisova Silvia, Kalavska Katarina, Karaba Marian, Benca Juraj, Smolkova Bozena, Mego Michal
Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska Cesta 9, 845 05 Bratislava, Slovakia.
Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, 841 04 Bratislava, Slovakia.
Cancers (Basel). 2020 May 1;12(5):1134. doi: 10.3390/cancers12051134.
A correlation between circulating tumor cells (CTCs) and monocytes in metastatic breast cancer (BC), where CTCs and monocyte-to-lymphocyte ratio (MLR) were predictors of overall survival (OS), was recently shown. Herein, we aimed to assess the association between CTCs and the complete blood count (CBC)-derived inflammation-based scores in 284 primary BC patients. CTCs were determined in CD45-depleted peripheral blood mononuclear cells by real time-PCR. This method allowed us to detect a subset of CTCs with an epithelial-to-mesenchymal transition phenotype (CTC EMT), previously associated with inferior outcomes in primary BC. In the present study, CTC EMT positivity (hazard ratio (HR) = 2.4; 95% CI 1.20-4.66, = 0.013) and elevated neutrophil-to-lymphocyte ratio (NLR) (HR = 2.20; 95% CI 1.07-4.55; = 0.033) were associated with shorter progression-free survival (PFS) in primary BC patients. Multivariate analysis showed that CTC EMT-positive patients with NLR ≥ 3 had 8.6 times increased risk of disease recurrence (95% CI 2.35-31.48, = 0.001) compared with CTC EMT-negative patients with NLR < 3. Similarly, disease recurrence was 13.14 times more likely in CTC EMT-positive patients with MLR ≥ 0.34 (95% CI 4.35-39.67, < 0.001). Given its low methodological and financial demands, the CBC-derived inflammation-based score determination could, after broader validation, significantly improve the prognostication of BC patients.
最近有研究表明,转移性乳腺癌(BC)中循环肿瘤细胞(CTC)与单核细胞之间存在相关性,其中CTC和单核细胞与淋巴细胞比值(MLR)是总生存期(OS)的预测指标。在此,我们旨在评估284例原发性BC患者中CTC与基于全血细胞计数(CBC)得出的炎症评分之间的关联。通过实时PCR在去除CD45的外周血单核细胞中检测CTC。该方法使我们能够检测到具有上皮-间质转化表型(CTC EMT)的CTC亚群,此前已发现其与原发性BC的不良预后相关。在本研究中,原发性BC患者中CTC EMT阳性(风险比(HR)=2.4;95%置信区间1.20 - 4.66,P = 0.013)和中性粒细胞与淋巴细胞比值(NLR)升高(HR = 2.20;95%置信区间1.07 - 4.55;P = 0.033)与无进展生存期(PFS)缩短相关。多变量分析显示,与NLR < 3的CTC EMT阴性患者相比,NLR≥3的CTC EMT阳性患者疾病复发风险增加8.6倍(95%置信区间2.35 - 31.48,P = 0.001)。同样,MLR≥0.34的CTC EMT阳性患者疾病复发的可能性是其13.14倍(95%置信区间4.35 - 39.67,P < 0.001)。鉴于基于CBC得出的炎症评分测定对方法和资金的要求较低,经过更广泛的验证后,它可能会显著改善BC患者的预后。