Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers?
Over the past 15 years, several biological and pathological characteristics proved their significance in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) prognostic stratification. However, the identification of new non-invasive disease biomarkers, relying on...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/11/2/253 |
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| author | Federica Lovisa Anna Garbin Sara Crotti Piero Di Battista Ilaria Gallingani Carlotta Caterina Damanti Anna Tosato Elisa Carraro Marta Pillon Erfan Mafakheri Filippo Romanato Enrico Gaffo Alessandra Biffi Stefania Bortoluzzi Marco Agostini Lara Mussolin |
| author_facet | Federica Lovisa Anna Garbin Sara Crotti Piero Di Battista Ilaria Gallingani Carlotta Caterina Damanti Anna Tosato Elisa Carraro Marta Pillon Erfan Mafakheri Filippo Romanato Enrico Gaffo Alessandra Biffi Stefania Bortoluzzi Marco Agostini Lara Mussolin |
| author_sort | Federica Lovisa |
| collection | DOAJ |
| description | Over the past 15 years, several biological and pathological characteristics proved their significance in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) prognostic stratification. However, the identification of new non-invasive disease biomarkers, relying on the most important disease mechanisms, is still necessary. In recent years, plasmatic circulating small extracellular vesicles (S-EVs) gathered great importance both as stable biomarker carriers and active players in tumorigenesis. In the present work, we performed a comprehensive study on the proteomic composition of plasmatic S-EVs of pediatric ALCL patients compared to healthy donors (HDs). By using a mass spectrometry-based proteomics approach, we identified 50 proteins significantly overrepresented in S-EVs of ALCL patients. Gene Ontology enrichment analysis disclosed cellular components and molecular functions connected with S-EV origin and vesicular trafficking, whereas cell adhesion, glycosaminoglycan metabolic process, extracellular matrix organization, collagen fibril organization and acute phase response were the most enriched biological processes. Of importance, consistently with the presence of nucleophosmin (NPM)-ALK fusion protein in ALCL cells, a topological enrichment analysis based on Reactome- and Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived networks highlighted a dramatic increase in proteins of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in ALCL S-EVs, which included heat shock protein 90-kDa isoform alpha 1 (HSP90AA1), osteopontin (SPP1/OPN) and tenascin C (TNC). These results were validated by Western blotting analysis on a panel of ALCL and HD cases. Further research is warranted to better define the role of these S-EV proteins as diagnostic and, possibly, prognostic parameters at diagnosis and for ALCL disease monitoring. |
| first_indexed | 2024-03-09T05:20:28Z |
| format | Article |
| id | doaj.art-be7300a7a39e4bddbdbac453fa7f663c |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-09T05:20:28Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-be7300a7a39e4bddbdbac453fa7f663c2023-12-03T12:41:17ZengMDPI AGDiagnostics2075-44182021-02-0111225310.3390/diagnostics11020253Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers?Federica Lovisa0Anna Garbin1Sara Crotti2Piero Di Battista3Ilaria Gallingani4Carlotta Caterina Damanti5Anna Tosato6Elisa Carraro7Marta Pillon8Erfan Mafakheri9Filippo Romanato10Enrico Gaffo11Alessandra Biffi12Stefania Bortoluzzi13Marco Agostini14Lara Mussolin15Maternal and Child Health Department, Padova University, 35128 Padova, ItalyMaternal and Child Health Department, Padova University, 35128 Padova, ItalyIstituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, ItalyMaternal and Child Health Department, Padova University, 35128 Padova, ItalyMaternal and Child Health Department, Padova University, 35128 Padova, ItalyMaternal and Child Health Department, Padova University, 35128 Padova, ItalyMaternal and Child Health Department, Padova University, 35128 Padova, ItalyPediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital, 35128 Padova, ItalyPediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital, 35128 Padova, ItalyDepartment of Physics and Astronomy, Padova University, 35131 Padova, ItalyDepartment of Physics and Astronomy, Padova University, 35131 Padova, ItalyDepartment of Molecular Medicine, Padova University, 35121 Padova, ItalyMaternal and Child Health Department, Padova University, 35128 Padova, ItalyDepartment of Molecular Medicine, Padova University, 35121 Padova, ItalyIstituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, ItalyMaternal and Child Health Department, Padova University, 35128 Padova, ItalyOver the past 15 years, several biological and pathological characteristics proved their significance in pediatric anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) prognostic stratification. However, the identification of new non-invasive disease biomarkers, relying on the most important disease mechanisms, is still necessary. In recent years, plasmatic circulating small extracellular vesicles (S-EVs) gathered great importance both as stable biomarker carriers and active players in tumorigenesis. In the present work, we performed a comprehensive study on the proteomic composition of plasmatic S-EVs of pediatric ALCL patients compared to healthy donors (HDs). By using a mass spectrometry-based proteomics approach, we identified 50 proteins significantly overrepresented in S-EVs of ALCL patients. Gene Ontology enrichment analysis disclosed cellular components and molecular functions connected with S-EV origin and vesicular trafficking, whereas cell adhesion, glycosaminoglycan metabolic process, extracellular matrix organization, collagen fibril organization and acute phase response were the most enriched biological processes. Of importance, consistently with the presence of nucleophosmin (NPM)-ALK fusion protein in ALCL cells, a topological enrichment analysis based on Reactome- and Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived networks highlighted a dramatic increase in proteins of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in ALCL S-EVs, which included heat shock protein 90-kDa isoform alpha 1 (HSP90AA1), osteopontin (SPP1/OPN) and tenascin C (TNC). These results were validated by Western blotting analysis on a panel of ALCL and HD cases. Further research is warranted to better define the role of these S-EV proteins as diagnostic and, possibly, prognostic parameters at diagnosis and for ALCL disease monitoring.https://www.mdpi.com/2075-4418/11/2/253ALCLsmall EVsproteomicsosteopontintenascin CHSP90 |
| spellingShingle | Federica Lovisa Anna Garbin Sara Crotti Piero Di Battista Ilaria Gallingani Carlotta Caterina Damanti Anna Tosato Elisa Carraro Marta Pillon Erfan Mafakheri Filippo Romanato Enrico Gaffo Alessandra Biffi Stefania Bortoluzzi Marco Agostini Lara Mussolin Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers? Diagnostics ALCL small EVs proteomics osteopontin tenascin C HSP90 |
| title | Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers? |
| title_full | Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers? |
| title_fullStr | Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers? |
| title_full_unstemmed | Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers? |
| title_short | Increased Tenascin C, Osteopontin and HSP90 Levels in Plasmatic Small Extracellular Vesicles of Pediatric ALK-Positive Anaplastic Large Cell Lymphoma: New Prognostic Biomarkers? |
| title_sort | increased tenascin c osteopontin and hsp90 levels in plasmatic small extracellular vesicles of pediatric alk positive anaplastic large cell lymphoma new prognostic biomarkers |
| topic | ALCL small EVs proteomics osteopontin tenascin C HSP90 |
| url | https://www.mdpi.com/2075-4418/11/2/253 |
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