Analysis of Melanoma Exosomes Identifies Potential Relapse Risk

A team of Spanish cancer researchers demonstrated that it was possible to detect the BRAFV600E mutation in exudative seroma-derived extracellular vesicles of patients following melanoma surgery, and its detection correlated with the likelihood that the patients would relapse.

Investigators at the Centro Nacional de Investigaciones Oncológicas (Madrid, Spain) based their study on the premise that liquid biopsies from cancer patients could have the potential to improve diagnosis and prognosis and that assessment of surrogate markers of tumor progression in circulating extracellular vesicles could be a powerful non-invasive approach in this setting.

To this end, they characterized extracellular vesicles purified from the lymphatic drainage also known as exudative seroma (ES) of stage III melanoma patients obtained after lymphadenectomy. Proteomic analysis showed that seroma-derived exosomes were enriched in proteins resembling melanoma progression.

Exosomes are cell-derived vesicles that are present in many and perhaps all biological fluids, including blood, urine, and cultured medium of cell cultures. The reported diameter of exosomes is between 30 and 100 nanometers, which is larger than low-density lipoproteins but much smaller than red blood cells. Exosomes, which contain RNA, proteins, lipids, and metabolites that are reflective of the cell type of origin, are either released from the cell when multivesicular bodies (MVBs) fuse with the plasma membrane, or they are released directly from the plasma membrane. Exosomes have specialized functions and play a key role in coagulation, intercellular signaling, and waste management.

In addition, the investigators found that the BRAFV600E mutation could be detected in ES-derived extracellular vesicles and its detection correlated with patients at risk of relapse.

"Our study has confirmed that, in melanoma patients, we can identify populations with higher risk of recurrence using a sensitive, accurate test of the exudative seroma," said senior author Dr. Héctor Peinado, head of the microenvironment and metastasis group at the Centro Nacional de Investigaciones Oncológicas. "Liquid biopsy applied to this seroma has revealed extracellular vesicles and circulating DNA with BRAF gene mutations associated with lower survival rates for melanoma patients. The method is performed in cooperation with clinical laboratories and could easily be applied in clinical practice. It only requires collecting seroma fluids and establishing the relevant protocol for collection, storage and analysis."

The study was published in the April 11, 2019, online edition of the Journal of Experimental Medicine.

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