Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Fatty acid and proteomic signatures of circulating CD81 positive small extracellular vesicles define the disease stage in melanoma patients

Version 1 : Received: 21 May 2021 / Approved: 24 May 2021 / Online: 24 May 2021 (15:07:09 CEST)

A peer-reviewed article of this Preprint also exists.

Paolino, G.; Huber, V.; Camerini, S.; Casella, M.; Macone, A.; Bertuccini, L.; Iosi, F.; Moliterni, E.; Cecchetti, S.; Ruspantini, I.; Chiarotti, F.; Vergani, E.; Lalli, L.; Raggi, C.; Di Biase, A.; Calvieri, S.; Mercuri, S.R.; Lugini, L.; Federici, C. The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients. Cancers 2021, 13, 4157. Paolino, G.; Huber, V.; Camerini, S.; Casella, M.; Macone, A.; Bertuccini, L.; Iosi, F.; Moliterni, E.; Cecchetti, S.; Ruspantini, I.; Chiarotti, F.; Vergani, E.; Lalli, L.; Raggi, C.; Di Biase, A.; Calvieri, S.; Mercuri, S.R.; Lugini, L.; Federici, C. The Fatty Acid and Protein Profiles of Circulating CD81-Positive Small Extracellular Vesicles Are Associated with Disease Stage in Melanoma Patients. Cancers 2021, 13, 4157.

Abstract

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is key to increase survival and therapeutic adjustment. Especially in stages II-IV biomarkers are urgently needed for adjuvant therapy purposes after resection and for treatment of metastatic patients. We here investigated if fatty acid (FA) and protein composition of small extracellular vesicles (sEV) deriving from plasma of 0-I, II, and III-IV stage melanoma patients (n=38) could reflect disease stage and thus function as biomarker. The subpopulation of sEV expressing CD81 (CD81sEV) was isolated by an ad hoc immune affinity technique from microvesicle-depleted plasma. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA and a decrease in Saturation Index (C18:0/C18:1), already detectable in early stages, distinguished patients’ from healthy donor CD81sEV. Proteomics (identifier PXD024434) detected an exclusive and significant increase of CD14, PON1, PON3 and APOA5 in stage II and a significant decrease of Rap1b in stage III-IV CD81sEV. The FA and proteomic stage dependent CD81sEV signature strengthens the potential of circulating sEV studies in providing discriminatory information for early diagnosis, prediction of metastatic behavior and follow up of melanoma patients.

Keywords

Melanoma patients; Small Extracellular Vesicles; Proteomics; Fatty acids; Biomarkers

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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