Bahnassy Abeer A, Saber Magdy M, Mahmoud Mohamed G, Abdellateif Mona S, Abd El-Mooti Samra Mohamed, Abd El-Fatah Rafaat M, Zekri Abdel-Rahman N, Salem Salem E
Tissue Culture and Cytogenetics Unit, Pathology Department, National Cancer Institute, Cairo University, 1 Fom El-Khalig Street, Cairo, Egypt.
Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt.
Mol Biol Rep. 2018 Dec;45(6):2025-2035. doi: 10.1007/s11033-018-4359-5. Epub 2018 Sep 18.
The aim of the current study was to assess the prognostic value of circulating tumor cells (CTCs) and their related markers at different points of chemotherapy regimens in metastatic breast cancer (MBC) patients. The impact of CTCs on progression free survival (PFS) and overall survival (OS) rates were also assessed. Peripheral blood samples were obtained from 66 female patients with MBC at different time intervals for evaluation of CTCs by flow cytometry (FC). cytokeratin 19 (CK19), mammaglobin, prolactin inducible peptide (PIP), aldehyde dehydrogenase 1 (ALDH1) and human chorionic gonadotropin (hCG) were also assessed by qRT-PCR. Analysis of different CTC levels (at 4, 5, and 6 cells/7 ml), showed statistically significant values at 4 cells/7 ml blood. The presence of baseline CTCs < 4 cells/7 ml, associated significantly with higher PFS (P value = 0.03). Patients showing a decrease in the CTCs level after treatment had significantly prolonged median PFS and OS rates compared to those whose CTCs level increased (P = 0.007 and P = 0.014; respectively). Mammaglobin, CK19, PIP, ALDH1 and hCG expression did not affect PFS or OS. However, patients with CTCs ≥ 4 at diagnosis had higher rates of progression compared to those with CTCs < 4 (1.9 times, P = 0.07), and who metastasized before 4 years showed a worse decrease outcomes (they were 2.4 time more progressed than those who metastasized after 4 years; P = 0.029). CTCs could be an independent prognostic and predictive biomarker for MBC patients' outcomes. Although none of the assessed genes (mammaglobin, CK19, PIP, ALDH1 and hCG) showed correlation with PFS or OS rates, further studies on a larger number of patients are required to validate the current results.
本研究的目的是评估转移性乳腺癌（MBC）患者化疗方案不同阶段循环肿瘤细胞（CTC）及其相关标志物的预后价值。同时也评估了CTC对无进展生存期（PFS）和总生存期（OS）率的影响。在不同时间间隔从66例女性MBC患者采集外周血样本，通过流式细胞术（FC）评估CTC。还通过qRT-PCR检测细胞角蛋白19（CK19）、乳腺珠蛋白、催乳素诱导肽（PIP）、醛脱氢酶1（ALDH1）和人绒毛膜促性腺激素（hCG）。对不同CTC水平（4、5和6个细胞/7毫升）的分析显示，在4个细胞/7毫升血液时具有统计学显著值。基线CTC＜4个细胞/7毫升与较高的PFS显著相关（P值=0.03）。与CTC水平升高的患者相比，治疗后CTC水平降低的患者中位PFS和OS率显著延长（分别为P = 0.007和P = 0.014）。乳腺珠蛋白、CK19、PIP、ALDH1和hCG表达不影响PFS或OS。然而，诊断时CTC≥4的患者进展率高于CTC＜4的患者（1.9倍，P = 0.07），且在4年前发生转移的患者预后较差（其进展速度比4年后发生转移的患者快2.4倍；P = 0.029）。CTC可能是MBC患者预后和预测的独立生物标志物。尽管所评估的基因（乳腺珠蛋白、CK19、PIP、ALDH1和hCG）均未显示与PFS或OS率相关，但需要对更多患者进行进一步研究以验证当前结果。
