Onstenk Wendy, Sieuwerts Anieta M, Mostert Bianca, Lalmahomed Zarina, Bolt-de Vries Joan B, van Galen Anne, Smid Marcel, Kraan Jaco, Van Mai, de Weerd Vanja, Ramírez-Moreno Raquel, Biermann Katharina, Verhoef Cornelis, Grünhagen Dirk J, IJzermans Jan N M, Gratama Jan W, Martens John W M, Foekens John A, Sleijfer Stefan
Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
Oncotarget. 2016 Sep 13;7(37):59058-59069. doi: 10.18632/oncotarget.10175.
CTCs are a promising alternative for metastatic tissue biopsies for use in precision medicine approaches. We investigated to what extent the molecular characteristics of circulating tumor cells (CTCs) resemble the liver metastasis and/or the primary tumor from patients with metastatic colorectal cancer (mCRC).
The CTC profiles were concordant with the liver metastasis in 17/23 patients (74%) and with the primary tumor in 13 patients (57%). The CTCs better resembled the liver metastasis in 13 patients (57%), and the primary tumor in five patients (22%). The strength of the correlations was not associated with clinical parameters. Nine genes (CDH1, CDH17, CDX1, CEACAM5, FABP1, FCGBP, IGFBP3, IGFBP4, and MAPT) displayed significant differential expressions, all of which were downregulated, in CTCs compared to the tissues in the 23 patients.
Patients were retrospectively selected from a prospective study. Using the CellSearch System, CTCs were enumerated and isolated just prior to liver metastasectomy. A panel of 25 CTC-specific genes was measured by RT-qPCR in matching CTCs, primary tumors, and liver metastases. Spearman correlation coefficients were calculated and considered as continuous variables with r=1 representing absolute concordance and r=-1 representing absolute discordance. A cut-off of r>0.1 was applied in order to consider profiles to be concordant.
In the majority of the patients, CTCs reflected the molecular characteristics of metastatic cells better than the primary tumors. Genes involved in cell adhesion and epithelial-to-mesenchymal transition were downregulated in the CTCs. Our results support the use of CTC characterization as a liquid biopsy for precision medicine.
循环肿瘤细胞（CTC）是转移性组织活检的一种有前景的替代方法，可用于精准医学。我们研究了转移性结直肠癌（mCRC）患者循环肿瘤细胞（CTC）的分子特征在多大程度上类似于肝转移灶和/或原发肿瘤。
23例患者中有17例（74%）的CTC特征与肝转移灶一致，13例（57%）与原发肿瘤一致。13例患者（57%）的CTC更类似于肝转移灶，5例患者（22%）的CTC更类似于原发肿瘤。相关性强度与临床参数无关。与23例患者的组织相比，9个基因（CDH1、CDH17、CDX1、CEACAM5、FABP1、FCGBP、IGFBP3、IGFBP4和MAPT）在CTC中显示出显著差异表达，所有这些基因均下调。
患者从一项前瞻性研究中回顾性选取。使用CellSearch系统，在肝转移灶切除术前对CTC进行计数和分离。通过逆转录定量聚合酶链反应（RT-qPCR）检测匹配的CTC、原发肿瘤和肝转移灶中一组25个CTC特异性基因。计算Spearman相关系数，并将其视为连续变量，r = 1表示绝对一致，r = -1表示绝对不一致。应用r>0.1的临界值来判断特征是否一致。
在大多数患者中，CTC比原发肿瘤更好地反映了转移细胞的分子特征。参与细胞黏附和上皮-间质转化的基因在CTC中下调。我们的结果支持将CTC特征分析作为精准医学的液体活检方法。
