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Fahrner M, Bronsert P, Fichtner-Feigl S, et al. Proteome biology of primary colorectal carcinoma and corresponding liver metastases. Neoplasia. 2021;23(12):1240-1251doi: 10.1016/j.neo.2021.10.005.
Fahrner, M., Bronsert, P., Fichtner-Feigl, S., Jud, A., & Schilling, O. (2021). Proteome biology of primary colorectal carcinoma and corresponding liver metastases. Neoplasia (New York, N.Y.), 23(12), 1240-1251. https://doi.org/10.1016/j.neo.2021.10.005
Fahrner, Matthias, et al. "Proteome biology of primary colorectal carcinoma and corresponding liver metastases." Neoplasia (New York, N.Y.) vol. 23,12 (2021): 1240-1251. doi: https://doi.org/10.1016/j.neo.2021.10.005
Fahrner M, Bronsert P, Fichtner-Feigl S, Jud A, Schilling O. Proteome biology of primary colorectal carcinoma and corresponding liver metastases. Neoplasia. 2021 Dec;23(12):1240-1251. doi: 10.1016/j.neo.2021.10.005. Epub 2021 Nov 09. PMID: 34768110; PMCID: PMC8591399.
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Neoplasia. 2021 Dec;23(12):1240-1251. doi: 10.1016/j.neo.2021.10.005. Epub 2021 Nov 09.

Proteome biology of primary colorectal carcinoma and corresponding liver metastases.

Neoplasia (New York, N.Y.)

Matthias Fahrner, Peter Bronsert, Stefan Fichtner-Feigl, Andreas Jud, Oliver Schilling

Affiliations

  1. Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; Faculty of Biology, Albert-Ludwigs-University Freiburg, Freiburg, Germany; Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg.
  2. Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; Tumorbank Comprehensive Cancer Center Freiburg, Medical Center - University of Freiburg; Core Facility Histopathology and Digital Pathology Freiburg, Medical Center - University of Freiburg.
  3. Department of General and Visceral Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  4. Department of General and Visceral Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany. Electronic address: [email protected].
  5. Institute for Surgical Pathology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany; BIOSS Centre for Biological Signaling Studies, University of Freiburg, D-79104 Freiburg, Germany.

PMID: 34768110 PMCID: PMC8591399 DOI: 10.1016/j.neo.2021.10.005

Abstract

Colorectal adenocarcinomas (CRC) are one of the most commonly diagnosed tumors worldwide. Colorectal adenocarcinomas primarily metastasize into the liver and (less often) into the peritoneum. Patients suffering from CRC-liver metastasis (CRC-LM) typically present with a dismal overall survival compared to non-metastasized CRC patients. The metastasis process and metastasis-promoting factors in patients with CRC are under intensive debate. However, CRC studies investigating the proteome biology are lacking. Formalin-fixed paraffin-embedded (FFPE) tissue specimens provide a valuable resource for comprehensive proteomic studies of a broad variety of clinical malignancies. The presented pilot study compares the proteome of primary CRC and patient-matched CRC-LM. The applied protocol allows a reproducible and straightforward identification and quantification of over 2,600 proteins within the dissected tumorous tissue. Subsequent unsupervised clustering reveals distinct proteome biologies of the primary CRC and the corresponding CRC-LM. Statistical analysis yields multiple differentially abundant proteins in either primary CRC or their corresponding liver metastases. A more detailed analysis of dysregulated biological processes suggests an active immune response in the liver metastases, including several proteins of the complement system. Proteins with structural roles, e.g. cytoskeleton organization or cell junction assembly appear to be less prominent in liver metastases as compared to primary CRC. Immunohistochemistry corroborates proteomic high expression levels of metabolic proteins in CRC-LM. We further assessed how the in vitro inhibition of two in CRC-LM enriched metabolic proteins affected cell proliferation and chemosensitivity. The presented proteomic investigation in a small clinical cohort promotes a more comprehensive understanding of the distinct proteome biology of primary CRC and their corresponding liver metastases.

Copyright © 2021. Published by Elsevier Inc.

Keywords: Colorectal cancer; liver metastases; mass spectrometry; proteomics

Conflict of interest statement

Conflict of interest statement The authors have declared no conflict of interest.

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