Evaluation of autophagy-related gene expression as prognostic factors in canine cutaneous mast cell tumours

• Grant number: 24/17508-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: February 01, 2025
• End date: October 31, 2029
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Ricardo de Francisco Strefezzi
• Grantee: Giovanna Pedroso Vicente
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Mast cell tumours (MCT) are one of the most frequent malignant neoplasms in dogs. The disease is usually treated for local control, with surgical excision, which adjuvant therapies, such radio and chemotherapy can complement. Autophagy is a physiological adaptative mechanism with intracellular autodegradation of nonfunctional molecules and organelles. In cancer, autophagy may promote cell death, consisting of a limiting factor for neoplastic proliferation, or contributing to energetic autosufficiency, as an adaptive factor, since cells are able to reuse the degraded materials. The aim of the present project is to characterize the autophagic process in canine cutaneous MCTs, investigate the expression of autophagy-related genes in cells resistant or not to radiotherapy, and investigate their prognostic value for this neoplasm. We hypothesise that the increased expression of autophagy-related genes increases the resistance of neoplastic mast cells to radiotherapy and, therefore, can be used as prognostic and, in the future, as predictive markers for this adjuvant therapy, potentially becoming new therapeutic targets. MCT samples will be cultured in vitro and subjected to radioresistance induction. Then, the expression patterns of autophagic genes will be analysed comparatively between resistant and non-resistant cell lines of canine MCT, mouse MCT and human mastocytosis. Protein expression will be validated and analysed in MCT samples in comparison with histological grades, disease-free interval and overall survival, for prognostic evaluation purposes.