title: Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer.
abstract: Cancer immunology is a growing field of research whose aim is to develop innovative therapies and diagnostic tests. Starting from the hypothesis that immune cells promptly respond to harmful stimuli, we used peripheral blood monocytes in order to characterise a distinct gene expression profile and to evaluate its potential as a candidate diagnostic biomarker in patients with colorectal cancer (CRC), a still unmet clinical need.
  
  
  
  We performed a case-control study including 360 peripheral blood monocyte samples from four European oncological centres and defined a gene expression profile specific to CRC. The robustness of the genetic profile and disease specificity were assessed in an independent setting.
  
  
  
  This screen returned 43 putative diagnostic markers, which we refined and validated in the confirmative multicentric analysis to 23 genes with outstanding diagnostic accuracy (area under the curve (AUC)=0.99 (0.99 to 1.00), Se=100.0% (100.0% to 100.0%), Sp=92.9% (78.6% to 100.0%) in multiple-gene receiver operating characteristic analysis). The diagnostic accuracy was robustly maintained in prospectively collected independent samples (AUC=0.95 (0.85 to 1.00), Se=92.6% (81.5% to 100.0%), Sp=92.3% (76.9% to 100.0%). This monocyte signature was expressed at early disease onset, remained robust over the course of disease progression, and was specific for the monocytic fraction of mononuclear cells. The gene modulation was induced specifically by soluble factors derived from transformed colon epithelium in comparison to normal colon or other cancer histotypes. Moreover, expression changes were plastic and reversible, as they were abrogated upon withdrawal of these tumour-released factors. Consistently, the modified set of genes reverted to normal expression upon curative treatment and was specific for CRC.
  
  
  
  Our study is the first to demonstrate monocyte plasticity in response to tumour-released soluble factors. The identified distinct signature in tumour-educated monocytes might be used as a candidate biomarker in CRC diagnosis and harbours the potential for disease follow-up and therapeutic monitoring.
authors: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven, Belgium Laboratory of Molecular Oncology and Angiogenesis, Department of Oncology, Vesalius Research Center, KU Leuven, Leuven, Belgium.
authors: Alexander
authors: A
authors: Hamm
authors: Digestive Oncology, University Hospitals Leuven and Department of Oncology, KU Leuven, Leuven, Belgium.
authors: Hans
authors: H
authors: Prenen
authors: Nucleomics Core, VIB, Leuven, Belgium.
authors: Wouter
authors: W
authors: Van Delm
authors: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven, Belgium Laboratory of Molecular Oncology and Angiogenesis, Department of Oncology, Vesalius Research Center, KU Leuven, Leuven, Belgium.
authors: Mario
authors: M
authors: Di Matteo
authors: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven, Belgium Laboratory of Molecular Oncology and Angiogenesis, Department of Oncology, Vesalius Research Center, KU Leuven, Leuven, Belgium.
authors: Mathias
authors: M
authors: Wenes
authors: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven, Belgium Laboratory of Molecular Oncology and Angiogenesis, Department of Oncology, Vesalius Research Center, KU Leuven, Leuven, Belgium.
authors: Estelle
authors: E
authors: Delamarre
authors: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors: Thomas
authors: T
authors: Schmidt
authors: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany Department of Visceral, Thoracic, and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
authors: Jürgen
authors: J
authors: Weitz
authors: Department of Oncology, San Filippo Neri, Rome, Italy.
authors: Roberta
authors: R
authors: Sarmiento
authors: Department of Oncology, San Filippo Neri, Rome, Italy.
authors: Angelo
authors: A
authors: Dezi
authors: Department of Oncology, San Filippo Neri, Rome, Italy.
authors: Giampietro
authors: G
authors: Gasparini
authors: Medical Oncology Clinic, Institut Jules Bordet, Brussels, Belgium.
authors: Françoise
authors: F
authors: Rothé
authors: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors: Robin
authors: R
authors: Schmitz
authors: Department of Abdominal Surgery, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors: André
authors: A
authors: D'Hoore
authors: VIB, Zwijnaarde, Belgium.
authors: Hannes
authors: H
authors: Iserentant
authors: Medical Oncology Clinic, Institut Jules Bordet, Brussels, Belgium.
authors: Alain
authors: A
authors: Hendlisz
authors: Laboratory of Molecular Oncology and Angiogenesis, Vesalius Research Center, VIB, Leuven, Belgium Laboratory of Molecular Oncology and Angiogenesis, Department of Oncology, Vesalius Research Center, KU Leuven, Leuven, Belgium.
authors: Massimiliano
authors: M
authors: Mazzone
mesh_terms: D000368:Aged; D001530:Belgium; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D055088:Early Detection of Cancer; D005062:European Union; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009000:Monocytes; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor
keywords: COLORECTAL CANCER; MACROPHAGES; MOLECULAR ONCOLOGY