title: Molecular characteristics of circulating tumor cells resemble the liver metastasis more closely than the primary tumor in metastatic colorectal cancer.
abstract: 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.
  
  
  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.
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Onstenk
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Anieta M
authors.initials: AM
authors.lastname: Sieuwerts
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Bianca
authors.initials: B
authors.lastname: Mostert
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Zarina
authors.initials: Z
authors.lastname: Lalmahomed
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Joan B
authors.initials: JB
authors.lastname: Bolt-de Vries
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: van Galen
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Smid
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Jaco
authors.initials: J
authors.lastname: Kraan
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Mai
authors.initials: M
authors.lastname: Van
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Vanja
authors.initials: V
authors.lastname: de Weerd
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ramírez-Moreno
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Grünhagen
authors.affiliation: Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jan N M
authors.initials: JN
authors.lastname: IJzermans
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Gratama
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.affiliation: Erasmus MC Cancer Institute, Department of Medical Oncology and Cancer Genomics Netherlands, Rotterdam, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
mesh_terms: D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000473:pathology*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D012189:Retrospective Studies; D046888:Tissue Array Analysis
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C490584:CDH17 protein, human; C491273:CDX1 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins
keywords: CTCs; CellSearch; circulating tumor cells; colorectal cancer; gene expression profiling