Merkley Seth D, Kang Huining, Brown-Glaberman Ursa, Marchetti Dario
Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Division of Epidemiology, Biostatistics and Preventive Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Cancers (Basel). 2025 Aug 21;17(16):2717. doi: 10.3390/cancers17162717.
: Breast cancer is the most commonly diagnosed cancer worldwide, with high rates of distant metastasis. While circulating tumor cells (CTCs) are the disseminatory units of metastasis and are indicative of a poor prognosis, CTC heterogeneity within individual patients, among breast cancer subtypes, and between primary and metastatic tumors within a patient obscures the relationship between CTCs and disease progression. EpCAM, its homolog Trop2, and a pan-Cytokeratin marker were evaluated to determine their contributions to CTC presence and clustering over the study period. We conducted a systematic longitudinal analysis of 51 breast cancer patients during the course of their treatment to deepen our understanding of CTC contributions to breast cancer progression. : 272 total blood samples from 51 metastatic breast cancer (mBC) patients were included in the study. Patients received diverse treatment schedules based on discretion of the practicing oncologist. Patients were monitored from July 2020 to March 2023, with blood samples collected at scheduled care appointments. Nucleated cells were isolated, imaged, and analyzed using Rarecyte technology, and statistical analysis was performed in R using the lmerTest and lme4 packages, as well as in Graphpad Prism version 10.4.1. : Both classical CTCs (DAPI+, EpCAM+, CK+, CD45- cells) and Trop2+ CTCs were detected in the blood of breast cancer patients. A high degree of correlation was found between CTC biomarkers, and CTC expression of EpCAM, Trop2, and the presence of CD45+ cells, all predicted cluster size, while Pan-CK did not. Furthermore, while analyses of biomarkers by receptor status revealed no significant differences among HR+, HER2+, and TNBC patients, longitudinal analysis found evidence for discrete trajectories of EpCAM, Trop2, and clustering between HR+ and HER2+ cancers after diagnosis of metastasis. : Correlation and longitudinal analysis revealed that EpCAM+, Trop2+, and CD45+ cells were predictive of CTC cluster presence and size, and highlighted distinct trajectories of biomarker change over time between HR+ and HER2+ cancers following metastatic diagnosis.
乳腺癌是全球最常被诊断出的癌症，远处转移率很高。虽然循环肿瘤细胞（CTC）是转移的播散单位，且预示着预后不良，但个体患者内、乳腺癌亚型之间以及患者原发肿瘤与转移肿瘤之间的CTC异质性掩盖了CTC与疾病进展之间的关系。对上皮细胞黏附分子（EpCAM）、其同源物滋养层细胞表面抗原2（Trop2）和一种泛细胞角蛋白标志物进行了评估，以确定它们在研究期间对CTC存在和聚集的作用。我们对51例乳腺癌患者在治疗过程中进行了系统的纵向分析，以加深我们对CTC在乳腺癌进展中作用的理解。：该研究纳入了51例转移性乳腺癌（mBC）患者的272份全血样本。患者根据执业肿瘤学家的判断接受了不同的治疗方案。从2020年7月至2023年3月对患者进行监测，在预定的护理预约时采集血样。使用Rarecyte技术分离、成像并分析有核细胞，使用lmerTest和lme4软件包在R中以及在GraphPad Prism 10.4.1版本中进行统计分析。：在乳腺癌患者血液中检测到了经典CTC（4′,6-二脒基-2-苯基吲哚阳性、EpCAM阳性、细胞角蛋白阳性、CD45阴性细胞）和Trop2阳性CTC。发现CTC生物标志物之间存在高度相关性，EpCAM、Trop2的CTC表达以及CD45阳性细胞的存在均能预测簇大小，而泛细胞角蛋白则不能。此外，虽然按受体状态对生物标志物的分析显示激素受体阳性（HR+）、人表皮生长因子受体2阳性（HER2+）和三阴性乳腺癌（TNBC）患者之间无显著差异，但纵向分析发现转移诊断后HR+和HER2+癌症之间EpCAM、Trop2及其聚集存在不同轨迹的证据。：相关性和纵向分析表明，EpCAM阳性、Trop2阳性和CD45阳性细胞可预测CTC簇的存在和大小，并突出了转移诊断后HR+和HER2+癌症之间生物标志物随时间变化的不同轨迹。
