title: Personalized Proteome Profiles of Healthy and Tumor Human Colon Organoids Reveal Both Individual Diversity and Basic Features of Colorectal Cancer.
abstract: Diseases at the molecular level are complex and patient dependent, necessitating development of strategies that enable precision treatment to optimize clinical outcomes. Organoid technology has recently been shown to have the potential to recapitulate the in vivo characteristics of the original individual's tissue in a three-dimensional in vitro culture system. Here, we present a quantitative mass-spectrometry-based proteomic analysis and a comparative transcriptomic analysis of human colorectal tumor and healthy organoids derived, in parallel, from seven patients. Although gene and protein signatures can be derived to distinguish the tumor organoid population from healthy organoids, our data clearly reveal that each patient possesses a distinct organoid signature at the proteomic level. We demonstrate that a personalized patient-specific organoid proteome profile can be related to the diagnosis of a patient and with future development contribute to the generation of personalized therapies.
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 Utrecht, the Netherlands.
authors.forename: Alba
authors.initials: A
authors.lastname: Cristobal
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 Utrecht, the Netherlands.
authors.forename: Henk W P
authors.initials: HWP
authors.lastname: van den Toorn
authors.affiliation: Princess Maxima Center for Pediatric Oncology, Uppsalalaan 8, 3584 Utrecht, Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: van de Wetering
authors.affiliation: Princess Maxima Center for Pediatric Oncology, Uppsalalaan 8, 3584 Utrecht, Netherlands; Hubrecht Institute, KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 Utrecht, Netherlands. Electronic address: h.clevers@hubrecht.eu.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 Utrecht, the Netherlands. Electronic address: a.j.r.heck@uu.nl.
authors.forename: Albert J R
authors.initials: AJR
authors.lastname: Heck
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics Group, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 Utrecht, the Netherlands; Netherlands Proteomics Center, Padualaan 8, 3584 Utrecht, the Netherlands; Department of Biochemistry, University of Oxford, New Biochemistry building, South Parks Road, Oxford OX1 3QU, UK; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford OX1 3TA, UK. Electronic address: shabaz.mohammed@chem.ox.ac.uk.
authors.forename: Shabaz
authors.initials: S
authors.lastname: Mohammed
mesh_terms: D003106:Colon / Q000378:metabolism* / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D009940:Organoids / Q000473:pathology*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D059467:Transcriptome / Q000235:genetics; D060449:Wnt Signaling Pathway
chemical_list: D020543:Proteome
keywords: colorectal cancer; mass spectrometry; organoids; proteomics