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

Author(s):Show less -

Garnica, Taismara K. ^[1] ; Lesbon, Jessika C. C. ^[1] ; Avila, Ana C. F. C. M. ^[2] ; Rochetti, Arina L. ^[1] ; Matiz, Oscar R. S. ^[3] ; Ribeiro, Roana C. S. ^[3] ; Zoppa, Aline ^[4] ; Nishiya, Adriana T. ^[4] ; Costa, Mirela T. ^[3] ; de Nardi, Andrigo B. ^[3] ; Argyle, David J. ^{[5, 6]} ; Strefezzi, Ricardo F. ^[1] ; Silveira, Juliano C. ^[2] ; Fukumasu, Heidge ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Anim Sci & Food Engn, Dept Vet Med, Lab Comparat & Translat Oncol LOCT, Pirassununga - Brazil

^[2] Univ Sao Paulo, Fac Anim Sci & Food Engn, Dept Vet Med, Lab Mol Morphophysiol & Dev LMMD, Pirassununga - Brazil

^[3] Sao Paulo State Univ Julio de Mesquita Filho UNES, Coll Agr & Vet Sci, Clin Vet Dept, Jaboticabal, SP - Brazil

^[4] Anhembi Morumbi Univ, Vet Hosp Anhembi Morumbi, Sao Paulo, SP - Brazil

^[5] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh, Midlothian - Scotland

^[6] Univ Edinburgh, Roslin Inst, Edinburgh, Midlothian - Scotland

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 NOV 23 2020.
• Web of Science Citations: 1

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 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. (AU)

• FAPESP's process: 14/02493-7 - Mammary tumors of dogs and the cancer stem cell theory: a comparative and translational approach
• Grantee: Heidge Fukumasu
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 15/21829-9 - Multi-user equipment approved in grant 2014/22887-0: Nanosight LM10
• Grantee: Juliano Coelho da Silveira
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 17/15406-3 - Extracellular vesicles as potencial predictive marker in canine multicentric lymphoma
• Grantee: Taismara Kustro Garnica
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/22887-0 - Cell-secreted vesicles containing miRNAs modulate epigenetic changes during in vitro culture of bovine gametes and embryos
• Grantee: Juliano Coelho da Silveira
• Support Opportunities: Research Grants - Young Investigators Grants