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Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas

2020; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41598-020-77366-7

2045-2322

Taismara Kustro Garnica, Jéssika Cristina Chagas Lesbon, Ana Clara Faquineli Cavalcante Mendes de Ávila, Arina Lázaro Rochetti, Oscar Rodrigo Sierra Matiz, Roana Cecília dos Santos Ribeiro, Aline Machado de Zoppa, Adriana Tomoko Nishiya, Mirela Tinucci‐Costa, Andrígo Barboza De Nardi, David J. Argyle, Ricardo de Francisco Strefezzi, Juliano Coelho da Silveira, Heidge Fukumasu,

Medical Imaging and Pathology Studies

Abstract 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 C omplete R esponse and 11 P rogressive D isease) 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.