Proteomic Analysis Identifies FNDC1, A1BG, and Antigen Processing Proteins Associated with Tumor Heterogeneity and Malignancy in a Canine Model of Breast Cancer
Cancers, vol. 13, pp. 5901
Abstract
New insights into the underlying biological processes of breast cancer are needed for the development of improved markers and treatments. The complex nature of mammary cancer in dogs makes it a great model to study cancer biology since they present a high degree of tumor heterogeneity. In search of disease-state biomarkers candidates, we applied proteomic mass spectrometry imaging in order to simultaneously detect histopathological and molecular alterations whilst preserving morphological integrity, comparing peptide expression between intratumor populations in distinct levels of differentiation. Peptides assigned to FNDC1, A1BG, and double-matching keratins 18 and 19 presented a higher intensity in poorly differentiated regions. In contrast, we observed a lower intensity of peptides matching calnexin, PDIA3, and HSPA5 in poorly differentiated cells, which enriched for protein folding in the endoplasmic reticulum and antigen processing, assembly, and loading of class I MHC. Over-representation of collagen metabolism, coagulation cascade, extracellular matrix components, cadherin-binding and cell adhesion pathways also distinguished cell populations. Finally, an independent validation showed FNDC1, A1BG, PDIA3, HSPA5, and calnexin as significant prognostic markers for human breast cancer patients. Thus, through a spatially correlated characterization of spontaneous carcinomas, we described key proteins which can be further validated as potential prognostic biomarkers.
Authors 9
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Affiliation as printed
Laboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga 13635-900, Brazil
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Leiden University Medical Center
Affiliation as printed
Center of Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Center of Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
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Affiliation as printed
Laboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga 13635-900, Brazil
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Leiden University Medical Center
Affiliation as printed
Center of Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Center of Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
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Affiliation as printed
Laboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga 13635-900, Brazil
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Leiden University Medical Center
Affiliation as printed
Center of Proteomics and Metabolomics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
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Heidge Fukumasu corresponding
Affiliation as printed
Laboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga 13635-900, Brazil
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