Satelli Arun, Mitra Abhisek, Brownlee Zachary, Xia Xueqing, Bellister Seth, Overman Michael J, Kopetz Scott, Ellis Lee M, Meng Qing H, Li Shulin
Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Surgical Oncology, Division of Surgery and Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2015 Feb 15;21(4):899-906. doi: 10.1158/1078-0432.CCR-14-0894. Epub 2014 Dec 16.
This study aimed to detect cell-surface vimentin (CSV) on the surface of epithelial-mesenchymal transitioned (EMT) circulating tumor cells (CTC) from blood of patients with epithelial cancers.
In this study, 101 patients undergoing postsurgery adjuvant chemotherapy for metastatic colon cancer were recruited. EMT CTCs were detected from blood of patients using the 84-1 monoclonal antibody against CSV as a marker. EMT CTCs isolated were characterized further using EMT-specific markers, fluorescent in situ hybridization, and single-cell mutation analysis.
Using the 84-1 antibody, we detected CSV exclusively on EMT CTCs from a variety of tumor types but not in the surrounding normal cells in the blood. The antibody exhibited very high specificity and sensitivity toward different epithelial cancer cells. With this antibody, we detected and enumerated EMT CTCs from patients. From our observations, we defined a cutoff of <5 or ≥5 EMT CTCs as the optimal threshold with respect to therapeutic response using ROC curves. Using this defined threshold, the presence of ≥5 EMT CTCs was associated with progressive disease, whereas patients with <5 EMT CTCs showed therapeutic response.
Taken together, the number of EMT CTCs detected correlated with the therapeutic outcome of the disease. These results establish CSV as a universal marker for EMT CTCs from a wide variety of tumor types and thus provide the foundation for emerging CTC detection technologies and for studying the molecular regulation of these EMT CTCs.
本研究旨在检测上皮癌患者血液中上皮-间质转化（EMT）循环肿瘤细胞（CTC）表面的细胞表面波形蛋白（CSV）。
本研究招募了101例接受转移性结肠癌术后辅助化疗的患者。使用抗CSV的84-1单克隆抗体作为标志物，从患者血液中检测EMT CTC。对分离出的EMT CTC进一步使用EMT特异性标志物、荧光原位杂交和单细胞突变分析进行表征。
使用84-1抗体，我们仅在来自多种肿瘤类型的EMT CTC上检测到CSV，而在血液中的周围正常细胞中未检测到。该抗体对不同的上皮癌细胞表现出非常高的特异性和敏感性。使用该抗体，我们检测并计数了患者的EMT CTC。根据我们的观察，利用ROC曲线，我们将<5或≥5个EMT CTC定义为治疗反应的最佳阈值。使用这个定义的阈值，≥5个EMT CTC的存在与疾病进展相关，而<5个EMT CTC的患者显示出治疗反应。
综上所述，检测到的EMT CTC数量与疾病的治疗结果相关。这些结果确立了CSV作为多种肿瘤类型EMT CTC的通用标志物，从而为新兴的CTC检测技术以及研究这些EMT CTC的分子调控提供了基础。
