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A reductionist approach using primary and metastatic cell-derived extracellular vesicles reveals hub proteins associated with oral cancer prognosis

ABSTRACT: 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 the role of EV cargo in OSCC metastasis. For that purpose, we used a reductionist approach to map the proteomic, miRNA, metabolomic, and lipidomic profiles of extracellular vesicles (EVs) derived from human primary tumor (SCC-9) cells and matched lymph node metastases (LN1) cells. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites, and 64 lipids differentially abundant between LN1- and SCC-9-derived EVs. A multi-omics integration identified 11 ‘hub proteins’ significantly decreased at the metastatic site compared to 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 metastatic EVs is correlated with reduced survival and tumor aggressiveness in cancer patients. 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.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Keratinocytes

DISEASE(S): Cancer

SUBMITTER: Ariane Busso Lopes

PROVIDER: ST001755 | MetabolomicsWorkbench | Mon Apr 26 00:00:00 BST 2021

REPOSITORIES: MetabolomicsWorkbench

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Reductionist approach using primary and metastatic cell-derived extracellular vesicles prospect proteins associated with oral cancer prognosis

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