Weber M, Fuchs D, Pöschel A, Beebe E, Garajova Z, Jarosch A, Kunz L, Wolski W, Opitz L, Guscetti F, Nolff MC, Markkanen E. Transcriptomic and proteomic profiling identifies feline fibrosarcoma as clinically amenable model for aggressive sarcoma subtypes. Neoplasia. 2024 Dec 14;60:101104. doi: 10.1016/j.neo.2024.101104. Epub ahead of print. PMID: 39681068.
(EveryCat funded studies EC23-034 and EC24-123)
Fibrosarcomas are a highly malignant tumor type in cats, and are often associated with previous injections, though spontaneous forms also occur. This study investigated the molecular biology of a set of fibrosarcoma’s in cats and compared them to other species in order to classify them further and determine possible therapeutic targets.
This was a retrospective study using residual tumor samples from naturally occurring disease in cats. Thirty primary tumors from 27 European Shorthair, two Maine Coon and one Persian mix cats were included, of which 17 were female (8 neutered) and 13 male (2 neutered). An injection-site origin could not be ruled out for any of the cases. However, in the absence of definite markers to differentiate between FISS and non-FISS FSA, all tumors were considered as ‘FSA’ without any definitively classified as FISS.
Samples collected from excised tissue were analyzed in a variety of ways, including proteomics, tandem liquid chromatography-mass spectroscopy, and RNA isolation and sequencing. Cell culture was performed, and survival analysis of affected cats was undertaken. Extensive data analysis was performed, the details of which are complex and beyond the scope of this summary.
Several genes were found to be over-represented in neoplastic tissue, including those related to the mitotic spindle, E2F targets, G2M checkpoint, inflammatory response, and Myc targets among others. There were also tumor-exclusive proteins detected in every single sample including: MARCKSL1, IKBIP, COPZ1, TIMP1, FAM50A and DPM3. Analysis of human tumors and canine samples found very similar markers, suggesting commonalities between the tumors in different species.
The authors also concluded there there are differences in immune and neuronal RNA expression patterns associated with tumor aggressiveness in feline FSA. These appear to be due to differences in the inflammatory response, (including the complement cascade), coagulation and DNA replication. They were further able to categorize feline FSA into three molecular subtypes which they termed: neuronal-like, fibroblastic and inflammatory, and theorized that these may influence clinical behavior. This identified feline FSA as a clinically amenable models for aggressive human STS.
This EveryCat funded study was a heavily molecular based project with extensive gene and proteome analysis. It was a basic science study that may allow further differentiation of tumor types and determining new therapeutic strategies. However, these will be the role of future projects and were not directly addressed by this paper. -MK
See Also
Dobromylskyj, M. (2022). Feline Soft Tissue Sarcomas: A Review of the Classification and Histological Grading, with Comparison to Human and Canine. Animals, 12(20), 2736. https://doi.org/10.3390/ani12202736