Research Papers:

Molecular characteristics of circulating tumor cells resemble the liver metastasis more closely than the primary tumor in metastatic colorectal cancer

Wendy Onstenk _, Anieta M. Sieuwerts, Bianca Mostert, Zarina Lalmahomed, Joan B. Bolt-de Vries, Anne van Galen, Marcel Smid, Jaco Kraan, Mai Van, Vanja de Weerd, Raquel Ramírez-Moreno, Katharina Biermann, Cornelis Verhoef, Dirk J. Grünhagen, Jan N.M. IJzermans, Jan W. Gratama, John W.M. Martens, John A. Foekens and Stefan Sleijfer

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Oncotarget. 2016; 7:59058-59069. https://doi.org/10.18632/oncotarget.10175

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Wendy Onstenk1, Anieta M. Sieuwerts1, Bianca Mostert1, Zarina Lalmahomed2, Joan B. Bolt-de Vries1, Anne van Galen1, Marcel Smid1, Jaco Kraan1, Mai Van1, Vanja de Weerd1, Raquel Ramírez-Moreno1, Katharina Biermann3, Cornelis Verhoef2, Dirk J. Grünhagen2, Jan N.M. IJzermans2, Jan W. Gratama1, John W.M. Martens1, John A. Foekens1, Stefan Sleijfer1

1Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands

2Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands

3Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands

Correspondence to:

Wendy Onstenk, email: [email protected]

Keywords: circulating tumor cells, CTCs, CellSearch, colorectal cancer, gene expression profiling

Received: April 06, 2016    Accepted: May 29, 2016    Published: June 20, 2016


Background: 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).

Results: 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 and Methods: 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.

Conclusions: 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.

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