title: Prediction of colorectal cancer diagnosis based on circulating plasma proteins.
abstract: Non-invasive detection of colorectal cancer with blood-based markers is a critical clinical need. Here we describe a phased mass spectrometry-based approach for the discovery, screening, and validation of circulating protein biomarkers with diagnostic value. Initially, we profiled human primary tumor tissue epithelia and characterized about 300 secreted and cell surface candidate glycoproteins. These candidates were then screened in patient systemic circulation to identify detectable candidates in blood plasma. An 88-plex targeting method was established to systematically monitor these proteins in two large and independent cohorts of plasma samples, which generated quantitative clinical datasets at an unprecedented scale. The data were deployed to develop and evaluate a five-protein biomarker signature for colorectal cancer detection.
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Surinova
authors.affiliation: Department of Statistics, Purdue University, West Lafayette, IN, USA.
authors.forename: Meena
authors.initials: M
authors.lastname: Choi
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Sha
authors.initials: S
authors.lastname: Tao
authors.affiliation: Department of Computer Science, Institute for Machine Learning, ETH Zurich, Zurich, Switzerland.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schüffler
authors.affiliation: Department of Statistics, Purdue University, West Lafayette, IN, USA.
authors.forename: Ching-Yun
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Statistics, Purdue University, West Lafayette, IN, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Clough
authors.affiliation: Department of Surgery, University Hospital in Olomouc, Olomouc, Czech Republic.
authors.forename: Kamil
authors.initials: K
authors.lastname: Vysloužil
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
authors.forename: Marta
authors.initials: M
authors.lastname: Khoylou
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Srovnal
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Mariette
authors.initials: M
authors.lastname: Matondo
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hüttenhain
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Weisser
authors.affiliation: Department of Computer Science, Institute for Machine Learning, ETH Zurich, Zurich, Switzerland.
authors.forename: Joachim M
authors.initials: JM
authors.lastname: Buhmann
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
authors.forename: Marián
authors.initials: M
authors.lastname: Hajdúch
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: Department of Statistics, Purdue University, West Lafayette, IN, USA Department of Computer Science, Purdue University, West Lafayette, IN, USA College of Science and College of Computer and Information Science, Northeastern University, Boston, MA, USA o.vitek@neu.edu aebersold@imsb.biol.ethz.ch.
authors.forename: Olga
authors.initials: O
authors.lastname: Vitek
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Faculty of Science, University of Zurich, Zurich, Switzerland o.vitek@neu.edu aebersold@imsb.biol.ethz.ch.
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D019411:Clinical Laboratory Techniques / Q000379:methods*; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010949:Plasma / Q000737:chemistry*
chemical_list: D014408:Biomarkers, Tumor
keywords: colorectal cancer; diagnostic protein biomarker; discovery‐driven and targeted proteomics