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The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients

SIMPLE SUMMARY: Early detection of cutaneous melanoma is the key to increasing survival and proper therapeutic adjustment, especially in stages II–IV. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) expressing CD81, derived from the plasma o...

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Autores principales: Paolino, Giovanni, Huber, Veronica, Camerini, Serena, Casella, Marialuisa, Macone, Alberto, Bertuccini, Lucia, Iosi, Francesca, Moliterni, Elisa, Cecchetti, Serena, Ruspantini, Irene, Chiarotti, Flavia, Vergani, Elisabetta, Lalli, Luca, Raggi, Carla, Di Biase, Antonella, Calvieri, Stefano, Mercuri, Santo Raffaele, Lugini, Luana, Federici, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392159/
https://www.ncbi.nlm.nih.gov/pubmed/34439311
http://dx.doi.org/10.3390/cancers13164157
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author Paolino, Giovanni
Huber, Veronica
Camerini, Serena
Casella, Marialuisa
Macone, Alberto
Bertuccini, Lucia
Iosi, Francesca
Moliterni, Elisa
Cecchetti, Serena
Ruspantini, Irene
Chiarotti, Flavia
Vergani, Elisabetta
Lalli, Luca
Raggi, Carla
Di Biase, Antonella
Calvieri, Stefano
Mercuri, Santo Raffaele
Lugini, Luana
Federici, Cristina
author_facet Paolino, Giovanni
Huber, Veronica
Camerini, Serena
Casella, Marialuisa
Macone, Alberto
Bertuccini, Lucia
Iosi, Francesca
Moliterni, Elisa
Cecchetti, Serena
Ruspantini, Irene
Chiarotti, Flavia
Vergani, Elisabetta
Lalli, Luca
Raggi, Carla
Di Biase, Antonella
Calvieri, Stefano
Mercuri, Santo Raffaele
Lugini, Luana
Federici, Cristina
author_sort Paolino, Giovanni
collection PubMed
description SIMPLE SUMMARY: Early detection of cutaneous melanoma is the key to increasing survival and proper therapeutic adjustment, especially in stages II–IV. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) expressing CD81, derived from the plasma of stage 0–I, II and III–IV melanoma patients, could reflect disease stage. Results showed a higher content of FA and differences in C18:0/C18:1 ratio, a marker of cell membrane fluidity, that distinguished patients’ CD81sEV from those of healthy donors (HD). By proteomic analysis (identifier PXD024434) we identified significant increases in CD14, PON1, PON3 and APOA5 in stage II CD81sEV compared to HD. In stage III–IV, CD81sEV’ RAP1B expression was decreased. These stage-related signatures may support the potential of sEV to provide information for early diagnosis, prediction of metastatic behavior, treatment and follow-up of melanoma patients. ABSTRACT: The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is fundamental to increasing survival and therapeutic adjustment. In stages II–IV especially, additional indications for adjuvant therapy purposes after resection and for treatment of metastatic patients are urgently needed. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) derived from the plasma of stage 0–I, II and III–IV melanoma patients (n = 38) could reflect disease stage. The subpopulation of sEV expressing CD81 EV marker (CD81sEV) was captured by an ad hoc immune affinity technique from plasma depleted of large EV. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA was detectable in patients with respect to healthy donors (HD). Moreover, a higher C18:0/C18:1 ratio, as a marker of cell membrane fluidity, distinguished early (stage 0–I) from late (III–IV) stages’ CD81sEV. Proteomics detected increases in CD14, PON1, PON3 and APOA5 exclusively in stage II CD81sEV, and RAP1B was decreased in stage III–IV CD81sEV, in comparison to HD. Our results suggest that stage dependent alterations in CD81sEV’ FA and protein composition may occur early after disease onset, strengthening the potential of circulating sEV as a source of discriminatory information for early diagnosis, prediction of metastatic behavior and following up of melanoma patients.
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spelling pubmed-83921592021-08-28 The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients Paolino, Giovanni Huber, Veronica Camerini, Serena Casella, Marialuisa Macone, Alberto Bertuccini, Lucia Iosi, Francesca Moliterni, Elisa Cecchetti, Serena Ruspantini, Irene Chiarotti, Flavia Vergani, Elisabetta Lalli, Luca Raggi, Carla Di Biase, Antonella Calvieri, Stefano Mercuri, Santo Raffaele Lugini, Luana Federici, Cristina Cancers (Basel) Article SIMPLE SUMMARY: Early detection of cutaneous melanoma is the key to increasing survival and proper therapeutic adjustment, especially in stages II–IV. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) expressing CD81, derived from the plasma of stage 0–I, II and III–IV melanoma patients, could reflect disease stage. Results showed a higher content of FA and differences in C18:0/C18:1 ratio, a marker of cell membrane fluidity, that distinguished patients’ CD81sEV from those of healthy donors (HD). By proteomic analysis (identifier PXD024434) we identified significant increases in CD14, PON1, PON3 and APOA5 in stage II CD81sEV compared to HD. In stage III–IV, CD81sEV’ RAP1B expression was decreased. These stage-related signatures may support the potential of sEV to provide information for early diagnosis, prediction of metastatic behavior, treatment and follow-up of melanoma patients. ABSTRACT: The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is fundamental to increasing survival and therapeutic adjustment. In stages II–IV especially, additional indications for adjuvant therapy purposes after resection and for treatment of metastatic patients are urgently needed. We investigated whether the fatty acid (FA) and protein compositions of small extracellular vesicles (sEV) derived from the plasma of stage 0–I, II and III–IV melanoma patients (n = 38) could reflect disease stage. The subpopulation of sEV expressing CD81 EV marker (CD81sEV) was captured by an ad hoc immune affinity technique from plasma depleted of large EV. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA was detectable in patients with respect to healthy donors (HD). Moreover, a higher C18:0/C18:1 ratio, as a marker of cell membrane fluidity, distinguished early (stage 0–I) from late (III–IV) stages’ CD81sEV. Proteomics detected increases in CD14, PON1, PON3 and APOA5 exclusively in stage II CD81sEV, and RAP1B was decreased in stage III–IV CD81sEV, in comparison to HD. Our results suggest that stage dependent alterations in CD81sEV’ FA and protein composition may occur early after disease onset, strengthening the potential of circulating sEV as a source of discriminatory information for early diagnosis, prediction of metastatic behavior and following up of melanoma patients. MDPI 2021-08-18 /pmc/articles/PMC8392159/ /pubmed/34439311 http://dx.doi.org/10.3390/cancers13164157 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Paolino, Giovanni
Huber, Veronica
Camerini, Serena
Casella, Marialuisa
Macone, Alberto
Bertuccini, Lucia
Iosi, Francesca
Moliterni, Elisa
Cecchetti, Serena
Ruspantini, Irene
Chiarotti, Flavia
Vergani, Elisabetta
Lalli, Luca
Raggi, Carla
Di Biase, Antonella
Calvieri, Stefano
Mercuri, Santo Raffaele
Lugini, Luana
Federici, Cristina
The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients
title The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients
title_full The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients
title_fullStr The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients
title_full_unstemmed The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients
title_short The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients
title_sort fatty acid and protein profiles of circulating cd81-positive small extracellular vesicles are associated with disease stage in melanoma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392159/
https://www.ncbi.nlm.nih.gov/pubmed/34439311
http://dx.doi.org/10.3390/cancers13164157
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