Feline mammary carcinoma as a model for human breast cancer: a proteomics study using formalin-fixed, paraffin-embedded tissue

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Abstract
Aim: Feline mammary carcinoma (FMC) shares strong histological and molecular similarities with human breast cancer, facilitating elucidation of pathophysiological tumor mechanisms, identification of prognostic indicators, discovery of biomarkers and therapeutic targets. This study characterized the proteome of two FMC subtypes, aggressive cribiform (CRIB) and less aggressive tubulopapillary (TUB), using formalin-fixed, paraffin-embedded (FFPE) tissue samples to identify aggressive biomarkers.Main methods: Twenty-one FMC samples (CRIB, n = 12, TUB, n = 9) were retrieved from a histological biobank. Following deparaffinization and digestion, proteomes were analyzed by shotgun nLC-MS/MS proteomics, Data were evaluated by principal component analysis (PCA), dendrogram, partial least squares discriminant analysis (PLS-DA), VIP score and Volcano plot (FDR < 0.05). Venn diagrams, String DB and ShinyGO for pathway enrichment.Key findings: A mong 976 identified proteins,113 were differentially abundant between subtypes. PCA showed partial overlap, but 15 key proteins were identified, with 14 elevated in CRIB. CRIB-specific proteins included AHNAK nucleoprotein, glycerol kinase, myosin-2, and an uncharacterized protein, TUB-specific proteins included glucosylceramidase beta 3, β2-glycoprotein-1, SEA domain-containing protein, and EF-hand domain-containing protein. T-complex protein 1 subunit alpha and reticulon-3 (both human breast cancer poor prognosis markers) iwere common to both subtypes. Enriched pathways involved metabolic, immune, and signaling networks.Significance: FFPE-based proteomics effectively identifies subtype-specific biomarkers and pathways, offering translational insights into FMC and human breast cancer.