PXD055198

PXD055198 is an original dataset announced via ProteomeXchange.

Title	The transcriptomic and proteomic landscape of feline fibrosarcoma and matched normal tissue
Description	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.
HostingRepository	PRIDE
AnnounceDate	2025-02-25
AnnouncementXML	Submission_2025-02-25_05:50:28.835.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Kunz
SpeciesList	scientific name: Felis catus (Cat) (Felis silvestris catus); NCBI TaxID: 9685;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-26 04:11:34	ID requested
⏵ 1	2025-02-25 05:50:29	announced

10.1016/J.NEO.2024.101104;

submitter keyword: disease model, laser-capture microdissection,Soft-tissue sarcoma, RNAsequencing, comparative oncology, tumor targeting, LC-MS/MS

Enni Markkanen
contact affiliation	Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zurich, 8057 Zürich, Switzerland
contact email	enni.markkanen@vetpharm.uzh.ch
lab head
Laura Kunz
contact affiliation	ETH
contact email	laura.kunz@fgcz.ethz.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055198
     1. Label: PRIDE project
     2. Name: The transcriptomic and proteomic landscape of feline fibrosarcoma and matched normal tissue