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

Taismara K Garnica; Jéssika C C Lesbon; Ana C F C M Ávila; Arina L Rochetti; Oscar R S Matiz; Roana C S Ribeiro; Aline Zoppa; Adriana T Nishiya; Mirela T Costa; Andrigo B de Nardi; David J Argyle; Ricardo F Strefezzi; Juliano C Silveira; Heidge Fukumasu

doi:10.1038/s41598-020-77366-7

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

Taismara K Garnica, Jéssika C C Lesbon, Ana C F C M Ávila, Arina L Rochetti, Oscar R S Matiz, Roana C S Ribeiro, Aline Zoppa, Adriana T Nishiya, Mirela T Costa, Andrigo B de Nardi, David J Argyle, Ricardo F Strefezzi, Juliano C Silveira, Heidge Fukumasu

Royal (Dick) School of Veterinary Studies

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	20371
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-77366-7
Publication status	Published - 23 Nov 2020

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Garnica, T. K., Lesbon, J. C. C., Ávila, A. C. F. C. M., Rochetti, A. L., Matiz, O. R. S., Ribeiro, R. C. S., Zoppa, A., Nishiya, A. T., Costa, M. T., de Nardi, A. B., Argyle, D. J., Strefezzi, R. F., Silveira, J. C., & Fukumasu, H. (2020). Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas. Scientific Reports, 10(1), 20371. https://doi.org/10.1038/s41598-020-77366-7

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title = "Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas",

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.",

author = "Garnica, {Taismara K} and Lesbon, {J{\'e}ssika C C} and {\'A}vila, {Ana C F C M} and Rochetti, {Arina L} and Matiz, {Oscar R S} and Ribeiro, {Roana C S} and Aline Zoppa and Nishiya, {Adriana T} and Costa, {Mirela T} and {de Nardi}, {Andrigo B} and Argyle, {David J} and Strefezzi, {Ricardo F} and Silveira, {Juliano C} and Heidge Fukumasu",

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Garnica, TK, Lesbon, JCC, Ávila, ACFCM, Rochetti, AL, Matiz, ORS, Ribeiro, RCS, Zoppa, A, Nishiya, AT, Costa, MT, de Nardi, AB, Argyle, DJ, Strefezzi, RF, Silveira, JC & Fukumasu, H 2020, 'Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas', Scientific Reports, vol. 10, no. 1, pp. 20371. https://doi.org/10.1038/s41598-020-77366-7

TY - JOUR

T1 - Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas

AU - Garnica, Taismara K

AU - Lesbon, Jéssika C C

AU - Ávila, Ana C F C M

AU - Rochetti, Arina L

AU - Matiz, Oscar R S

AU - Ribeiro, Roana C S

AU - Zoppa, Aline

AU - Nishiya, Adriana T

AU - Costa, Mirela T

AU - de Nardi, Andrigo B

AU - Argyle, David J

AU - Strefezzi, Ricardo F

AU - Silveira, Juliano C

AU - Fukumasu, Heidge

PY - 2020/11/23

Y1 - 2020/11/23

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-020-77366-7

DO - 10.1038/s41598-020-77366-7

M3 - Article

C2 - 33230132

SN - 2045-2322

VL - 10

SP - 20371

JO - Scientific Reports

JF - Scientific Reports

IS - 1

ER -

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

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