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The transcriptomic and proteomic landscape of feline fibrosarcoma and matched normal tissue

ABSTRACT: Fibrosarcomas (FSA) are rare malignant soft tissue tumors characterized by low chemo- and radiosensitivity. Development of novel treatment strategies for human FSA is hindered by the low incidence and the absence of suitable clinical models. Interestingly, aggressive FSA occur more frequently in domestic cats, hence potentially representing a clinically amenable model to assess novel therapies such as targeted imaging or theranostics. However, a lack of molecular characterization of FSA and adjacent normal tissue (NT) in both species hinders identification of tumor-specific targets and undermines the translational potential of feline FSA. Combining laser-capture microdissection, RNA sequencing and LC-MS/MS, we perform comprehensive profiling of 30 feline FSA and matched skeletal muscle, adipose and connective tissue. Clear inter-tissue differences allow identification of significantly upregulated and tumor-exclusive features that represent potential targets for diagnostic and therapeutic approaches. While feline FSA are characterized by hyperactive EIF2, TP53 and MYC signaling, immune-related and neuronal pathways emerge as modulators of tumor aggressiveness and immunosuppression. A high degree of molecular similarity with canine and human FSA allows identification of conserved cross-species tumor targets. Significant enrichment in DNA repair pathways in feline FSA are shown to be associated with aggressive clinical behavior in human STS. Finally, we leverage the molecular profiles to identify vulnerabilities, including sensitivity to ATR and PARP inhibition as potential treatment for feline FSA. In conclusion, this detailed landscape provides a rich resource to identify target candidates and therapeutic vulnerabilities within and across species and supports feline FSA as relevant models for the human disease.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Felis Catus (cat) (felis Silvestris Catus)

TISSUE(S): Muscle, Ccd-18co Cell, Connective Tissue, Adipose Tissue

DISEASE(S): Fibrosarcoma

SUBMITTER: Laura Kunz

LAB HEAD: Enni Markkanen

PROVIDER: PXD055198 | Pride | 2025-02-25

REPOSITORIES: Pride

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	20210917_002_S314874_MN32-M.raw	Raw
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	20210917_004_S314845_MN23-M.raw	Raw
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	20210917_007_S314867_MN30-M.raw	Raw

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The transcriptomic and proteomic landscape of feline fibrosarcoma and matched normal tissue

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