Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse

Abstract Colorectal cancer molecular signatures derived from omics data can be employed to stratify CRC patients and aid decisions about therapies or evaluate prognostic outcome. However, molecular biomarkers for identification of patients at increased risk of disease relapse are currently lacking....

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Main Authors: Ana Martinez-Val, Leander Van der Hoeven, Dorte B Bekker-Jensen, Margarita Melnikova Jørgensen, Jesper Nors, Giulia Franciosa, Claus L Andersen, Jesper B Bramsen, Jesper V Olsen
Format: Article
Language:English
Published: Springer Nature 2025-04-01
Series:Molecular Systems Biology
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Online Access:https://doi.org/10.1038/s44320-025-00102-8
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author Ana Martinez-Val
Leander Van der Hoeven
Dorte B Bekker-Jensen
Margarita Melnikova Jørgensen
Jesper Nors
Giulia Franciosa
Claus L Andersen
Jesper B Bramsen
Jesper V Olsen
author_facet Ana Martinez-Val
Leander Van der Hoeven
Dorte B Bekker-Jensen
Margarita Melnikova Jørgensen
Jesper Nors
Giulia Franciosa
Claus L Andersen
Jesper B Bramsen
Jesper V Olsen
author_sort Ana Martinez-Val
collection DOAJ
description Abstract Colorectal cancer molecular signatures derived from omics data can be employed to stratify CRC patients and aid decisions about therapies or evaluate prognostic outcome. However, molecular biomarkers for identification of patients at increased risk of disease relapse are currently lacking. Here, we present a comprehensive multi-omics analysis of a Danish colorectal cancer tumor cohort composed of 412 biopsies from tumors of 371 patients diagnosed at TNM stage II or III. From mass spectrometry-based patient proteome profiles, we classified the tumors into four molecular subtypes, including a mesenchymal-like subtype. As the mesenchymal-rich tumors are known to represent the most invasive and metastatic phenotype, we focused on the protein signature defining this subtype to evaluate their potential as relapse risk markers. Among signature-specific proteins, we followed-up Caveolae-Associated Protein-1 (CAVIN1) and demonstrated its role in tumor progression in a 3D in vitro model of colorectal cancer. Compared to previous omics analyses of CRC, our multi-omics classification provided deeper insights into EMT in cancer cells with stronger correlations with risk of relapse.
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spelling doaj-art-6bb2adc6f342410cb0adc940014499c72025-08-20T04:01:43ZengSpringer NatureMolecular Systems Biology1744-42922025-04-0121777680610.1038/s44320-025-00102-8Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapseAna Martinez-Val0Leander Van der Hoeven1Dorte B Bekker-Jensen2Margarita Melnikova Jørgensen3Jesper Nors4Giulia Franciosa5Claus L Andersen6Jesper B Bramsen7Jesper V Olsen8Novo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of CopenhagenInstitute of Pathology, Randers Regional HospitalDepartment of Clinical Medicine, Aarhus University HospitalNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Clinical Medicine, Aarhus University HospitalDepartment of Clinical Medicine, Aarhus University HospitalNovo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of CopenhagenAbstract Colorectal cancer molecular signatures derived from omics data can be employed to stratify CRC patients and aid decisions about therapies or evaluate prognostic outcome. However, molecular biomarkers for identification of patients at increased risk of disease relapse are currently lacking. Here, we present a comprehensive multi-omics analysis of a Danish colorectal cancer tumor cohort composed of 412 biopsies from tumors of 371 patients diagnosed at TNM stage II or III. From mass spectrometry-based patient proteome profiles, we classified the tumors into four molecular subtypes, including a mesenchymal-like subtype. As the mesenchymal-rich tumors are known to represent the most invasive and metastatic phenotype, we focused on the protein signature defining this subtype to evaluate their potential as relapse risk markers. Among signature-specific proteins, we followed-up Caveolae-Associated Protein-1 (CAVIN1) and demonstrated its role in tumor progression in a 3D in vitro model of colorectal cancer. Compared to previous omics analyses of CRC, our multi-omics classification provided deeper insights into EMT in cancer cells with stronger correlations with risk of relapse.https://doi.org/10.1038/s44320-025-00102-8Colorectal CancerProteomicsTumor RelapseCAVIN1
spellingShingle Ana Martinez-Val
Leander Van der Hoeven
Dorte B Bekker-Jensen
Margarita Melnikova Jørgensen
Jesper Nors
Giulia Franciosa
Claus L Andersen
Jesper B Bramsen
Jesper V Olsen
Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse
Molecular Systems Biology
Colorectal Cancer
Proteomics
Tumor Relapse
CAVIN1
title Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse
title_full Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse
title_fullStr Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse
title_full_unstemmed Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse
title_short Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse
title_sort proteomics of colorectal tumors identifies the role of cavin1 in tumor relapse
topic Colorectal Cancer
Proteomics
Tumor Relapse
CAVIN1
url https://doi.org/10.1038/s44320-025-00102-8
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