Dong Xiu, Ma Yongsu, Zhao Xudong, Tian Xiaodong, Sun Yulin, Yang Yinmo, Zhao Xiaohang
State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of General Surgery, Peking University First Hospital, Beijing, China.
Ann Transl Med. 2020 Jun;8(11):676. doi: 10.21037/atm-20-782.
The spatial heterogeneity of epithelial to mesenchymal transition (EMT)-related circulating tumor cells (CTCs) within the circulatory system and its potential clinical relevance remain unclear in pancreatic cancer (PC) patients. We aimed to map the distribution of EMT-related CTCs along the spreading pathway and investigate the prognostic significance due to the potential spatial heterogeneity in the count and phenotypic properties of CTCs.
Both portal vein (PoV) and peripheral vein (PV) blood samples were collected from 39 PC patients. CTCs were isolated by using a CD45 negative enrichment method, and EMT-related phenotypes in CTCs were analyzed by 4-channel immunofluorescence. The correlations of CTCs with patient characteristics and recurrence-free survival (RFS) were analyzed.
Both the number {median CTC total count, 10 [6-16] in PoV 5 [1-7] in PV per mL, P<0.0001} and EMT status of CTCs [median mesenchymal CTC (M-CTC) percentage, 0.33 (0.13-0.52) in PoV 0.2 (0-0.4) in PV, P=0.0211] showed significant spatial heterogeneity during dissemination from the PoV to the PV. Univariate analysis adjusting for patient age and sex revealed that CTC total count and M-CTC percentage in PoV samples could be risk factors for RFS in PC patients (P=0.003 and P=0.001, respectively), and ROC curve analysis found that both of these factors had good performance in distinguishing patients with early distant recurrence (within 6 months), with the optimal cut-off values of 14 cells/mL (AUROC =0.893, sensitivity =0.857, specificity =0.813, P=0.001) and 0.545 (AUROC =0.795, sensitivity =0.714, specificity =0.906, P=0.016), respectively.
Multivascular assessment of EMT-related CTCs suggested profound dynamic alterations in total count and phenotypes during dissemination, and the spatial heterogeneity of CTCs in circulation could help establish novel prognosis markers in PC patients.
在胰腺癌（PC）患者中，循环系统内上皮-间质转化（EMT）相关循环肿瘤细胞（CTC）的空间异质性及其潜在的临床相关性仍不清楚。我们旨在描绘EMT相关CTC沿扩散途径的分布，并研究由于CTC数量和表型特性的潜在空间异质性而产生的预后意义。
从39例PC患者中采集门静脉（PoV）和外周静脉（PV）血样。采用CD45阴性富集法分离CTC，并通过4通道免疫荧光分析CTC中的EMT相关表型。分析CTC与患者特征及无复发生存期（RFS）的相关性。
CTC的数量{中位数CTC总数，PoV中每毫升为10[6-16]个，PV中为5[1-7]个，P<0.0001}和EMT状态[中位数间充质CTC（M-CTC）百分比，PoV中为0.33（0.13-0.52），PV中为0.2（0-0.4），P=0.0211]在从PoV扩散到PV的过程中均显示出显著的空间异质性。对患者年龄和性别进行校正的单因素分析显示，PoV样本中的CTC总数和M-CTC百分比可能是PC患者RFS的危险因素（分别为P=0.003和P=0.001），ROC曲线分析发现这两个因素在区分早期远处复发（6个月内）患者方面均具有良好的性能，最佳截断值分别为14个细胞/毫升（AUROC=0.893，敏感性=0.857，特异性=0.813，P=0.001）和0.545（AUROC=0.795，敏感性=0.714，特异性=0.906，P=0.016）。
对EMT相关CTC的多血管评估表明，在扩散过程中总数和表型存在深刻的动态变化，循环中CTC 的空间异质性有助于建立PC患者的新预后标志物。
