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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.

SUBMITTER: Garnica TK

PROVIDER: S-EPMC7683601 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Garnica Taismara K TK Lesbon Jéssika C C JCC Ávila Ana C F C M ACFCM Rochetti Arina L AL Matiz Oscar R S ORS Ribeiro Roana C S RCS Zoppa Aline A Nishiya Adriana T AT Costa Mirela T MT de Nardi Andrigo B AB Argyle David J DJ Strefezzi Ricardo F RF Silveira Juliano C JC Fukumasu Heidge H

Scientific reports 20201123 1

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 s ...[more]

PMID: 33230132

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Project description:Extracellular vesicles (EVs) are abundantly released into the systemic circulation, where they show remarkable stability and harbor molecular constituents that provide biochemical information about their cells of origin. Due to this characteristic, EVs are attracting increasing attention as a source of circulating biomarkers for cancer liquid biopsy and personalized medicine. Despite this potential, none of the discovered biomarkers has entered the clinical practice so far, and novel approaches for the label-free characterization of EVs are highly demanded. In this regard, Fourier Transform Infrared Spectroscopy (FTIR) has great potential as it provides a quick, reproducible, and informative biomolecular fingerprint of EVs. In this pilot study, we investigated, for the first time in the literature, the capability of FTIR spectroscopy to distinguish between EVs extracted from sera of cancer patients and controls based on their mid-IR spectral response. For this purpose, EV-enriched suspensions were obtained from the serum of patients diagnosed with Hepatocellular Carcinoma (HCC) of nonviral origin and noncancer subjects. Our data point out the presence of statistically significant differences in the integrated intensities of major mid-IR absorption bands, including the carbohydrate and nucleic acids band, the protein amide I and II bands, and the lipid CH stretching band. Additionally, we used Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) for the automated classification of spectral data according to the shape of specific mid-IR spectral signatures. The diagnostic performances of the proposed spectral biomarkers, alone and combined, were evaluated using multivariate logistic regression followed by a Receiving Operator Curve analysis, obtaining large Areas Under the Curve (AUC = 0.91, 95% CI 0.81–1.0). Very interestingly, our analyses suggest that the discussed spectral biomarkers can outperform the classification ability of two widely used circulating HCC markers measured on the same groups of subjects, namely alpha-fetoprotein (AFP), and protein induced by the absence of vitamin K or antagonist-II (PIVKA-II).

Dataset Information

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

Publications

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

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