A Reductionist Approach Using Primary and Metastatic Cell–Derived Extracellular Vesicles Reveals Hub Proteins Associated with Oral Cancer Prognosis
| العنوان: | A Reductionist Approach Using Primary and Metastatic Cell–Derived Extracellular Vesicles Reveals Hub Proteins Associated with Oral Cancer Prognosis |
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| المؤلفون: | Ricardo D. Coletta, Adriana Franco Paes Leme, Juliana A. Aricetti, Kelly A. Dryden, Jay W. Fox, Carolina Moretto Carnielli, Diego Mauricio Riaño-Pachón, Bianca Alves Pauletti, Rute Alves Pereira e Costa, Romênia R. Domingues, Edgard Graner, Flavia Vischi Winck, Fábio Malta de Sá Patroni, Ana Oliveira, Ariane Fidelis Busso-Lopes, Camila Caldana, Daniela C. Granato |
| المصدر: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Molecular & Cellular Proteomics : MCP |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Proteomics, HNCDB, Head and Neck Cancer Database, HNSCC, head and neck squamous cell carcinoma, Biochemistry, Analytical Chemistry, Metastasis, Mice, AUC, area under the curve, PC, phosphatidylcholine, LMPD, LIPID MAPS Proteome Database, NTA, nanoparticle tracking analysis, Lymph node, mass spectrometry, Mouth neoplasm, 0303 health sciences, lymph node metastasis, 030302 biochemistry & molecular biology, Extracellular vesicle, Prognosis, Primary tumor, oral squamous cell carcinoma, medicine.anatomical_structure, Biology, PE, phosphatidylethanolamine, KEGG, Kyoto Encyclopedia of Genes and Genomes, Cell Line, Extracellular Vesicles, 03 medical and health sciences, EV, extracellular vesicle, GO, Gene Ontology, microRNA, medicine, Animals, Humans, Metabolomics, OSCC, oral squamous cell carcinoma, Molecular Biology, 030304 developmental biology, PCA, principal component analysis, Research, mouth neoplasms, THCA, thyroid cancer, Cancer, multi-omics, medicine.disease, Head and neck squamous-cell carcinoma, ROC, receiver operating characteristic, MicroRNAs, stomatognathic diseases, Cancer research, TCGA, The Cancer Genome Atlas, integrative analysis, PROGNÓSTICO |
| الوصف: | Oral squamous cell carcinoma (OSCC) has high mortality rates that are largely associated with lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Extracellular vesicles (EVs) are membrane-bound particles that play a role in intercellular communication and impact cancer development and progression. Thus, profiling EVs would be of great significance to decipher their role in OSCC metastasis. For that purpose, we used a reductionist approach to map the proteomic, miRNA, metabolomic, and lipidomic profiles of EVs derived from human primary tumor (SCC-9) cells and matched lymph node metastatic (LN1) cells. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites, and 63 lipids differentially abundant between LN1 cell– and SCC-9 cell–derived EVs. A multi-omics integration identified 11 ‘hub proteins’ significantly decreased at the metastatic site compared with primary tumor–derived EVs. We confirmed the validity of these findings with analysis of data from multiple public databases and found that low abundance of seven ‘hub proteins’ in EVs from metastatic lymph nodes (ALDH7A1, CAD, CANT1, GOT1, MTHFD1, PYGB, and SARS) is correlated with reduced survival and tumor aggressiveness in patients with cancer. In summary, this multi-omics approach identified proteins transported by EVs that are associated with metastasis and which may potentially serve as prognostic markers in OSCC. Graphical Abstract Highlights • Proteomic, miRNA, metabolomic, and lipidomic profiles were mapped in oral cancer EVs. • The molecular profile of EVs was associated with the lymph node metastatic phenotype. • A multi-omics integrative analysis revealed 11 highly connected ‘hub proteins.’ • ‘Hub proteins’ from EVs are candidates as prognostic markers in oral cancer. In Brief A multi-omics strategy was used to map the proteome, miRNA, metabolome, and lipidome of EVs derived from human primary tumor (SCC-9) cells and matched lymph node metastatic (LN1) cells. Differentially abundant molecules associated with the metastatic phenotype were enriched for key processes and pathways. An integrative analysis revealed 11 ‘hub proteins’ that are correlated with reduced survival and tumor aggressiveness in patients with cancer according to public databases. These EV molecules are candidates as prognostic markers in oral cancer. |
| تدمد: | 1535-9476 |
| DOI: | 10.1016/j.mcpro.2021.100118 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed5ef7e9b4cba4e1d8ce1bb05ea4e9d3 https://doi.org/10.1016/j.mcpro.2021.100118 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ed5ef7e9b4cba4e1d8ce1bb05ea4e9d3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15359476 |
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| DOI: | 10.1016/j.mcpro.2021.100118 |