RESUMEN

Lymphoma is the most common type of canine hematological malignancy where the multicentric (cMCL) form accounts for 75% of all cases. The standard treatment is the CHOP chemotherapy protocols that include cyclophosphamide, doxorubicin, vincristine and prednisone, where the majority of dogs achieve complete/partial response; however, it is very important to predict non-responsive cases to improve treatment and to develop new targeted therapies. Here we evaluate a liquid biopsy approach based on serum Small Extracellular Vesicles enriched for exosomes (SEVs) to predict cMCL chemotherapy response. Nineteen dogs at the end of the 19-week chemotherapy protocol (8 Complete Response and 11 Progressive Disease) were evaluated for serum SEVs size, concentration and screened for 95 oncomirs. PD patients had higher SEVs concentration at the diagnosis than CR patients (P = 0.034). The ROC curve was significant for SEVs concentration to predict the response to CHOP (AUC = 0.8011, P = 0.0287). A potential molecular signature based on oncomirs from SEVs (caf-miR-205, caf-miR-222, caf-mir-20a and caf-miR-93) is proposed. To the best of our knowledge, this is the first study demonstrating the potential of a liquid biopsy based on SEVs and their miRNAs content to predict the outcome of chemotherapy for canine multicentric lymphomas.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Biomarcadores de Tumor/genética , Enfermedades de los Perros/tratamiento farmacológico , Vesículas Extracelulares/genética , Linfoma/tratamiento farmacológico , Linfoma/veterinaria , MicroARNs/genética , Animales , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Ciclofosfamida/farmacología , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/genética , Enfermedades de los Perros/mortalidad , Perros , Doxorrubicina/farmacología , Vesículas Extracelulares/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Biopsia Líquida , Linfoma/genética , Linfoma/mortalidad , Masculino , MicroARNs/sangre , Fosfatidilinositol 3-Quinasas/sangre , Fosfatidilinositol 3-Quinasas/genética , Prednisona/farmacología , Isoformas de Proteínas/sangre , Isoformas de Proteínas/genética , Proteínas Proto-Oncogénicas c-kit/sangre , Proteínas Proto-Oncogénicas c-kit/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/sangre , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Recurrencia , Factor de Células Madre/sangre , Factor de Células Madre/genética , Análisis de Supervivencia , Resultado del Tratamiento , Vincristina/farmacología