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

Oral squamous cell carcinoma (OSCC) shows high mortality rates that are largely associated with the presence of lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Here, we used a reductionist approach mapping the proteomic, miRNA, metabolomic and lipidomic profiles of extracellular vesicles (EVs) from human primary tumor (SCC-9 cells) and matched lymph node metastasis (LN1 cells) to explore the role of EV cargo in OSCC metastasis. 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 indicated 11 ‘hub proteins’ significantly modulated in the metastatic site when compared to primary site-derived EVs, seven of them correlated with aggressiveness in cancer patients. The multi-omics approach allowed the prospection of proteins transported by EVs that potentially serves as prognostic markers in OSCC.