Investigation of Extracellular Vesicles Melanoma: Insights into Biomarkers from the Tumour Microenvironment and Circulation

This thesis investigates reliable biomarkers in melanoma, an aggressive skin cancer, for better risk assessment, prediction of treatment response, and prognostication. Current methods struggle to accurately identify patients at risk of progression who could benefit from advanced treatments. The research explores Extracellular Vesicles (EVs) from melanoma patients and healthy individuals, using proteomics and metabolomics analysis. Machine learning was used to create proteo-metabolomic signatures, effectively distinguishing between patients with melanoma and healthy individuals, and also between primary and advanced melanoma stages with over 70% accuracy. The research identified correlations between the tumour's genetic activity and plasma EV makeup through gene expression profiling. This process emphasised the role of chemokine signalling in melanoma progression due to the increased expression of chemokine ligands and receptors. Laboratory tests showed that EVs derived from melanoma alter the chemokine secretion in normal skin cells, suggesting a role in reshaping the tumour environment. It was also found that EVs can carry chemokines, such as CXCL8, with lower levels found in advanced melanoma. In parallel, the study investigated canine melanoma's relevance to human melanoma using a comparative oncology approach. Canine plasma derived EVs showed significant similarities to human EVs, and gene profiling of canine melanoma tissue revealed altered pathways involved in development. Assessment of stakeholder understanding and research priorities within this field identified areas needing improved engagement. In summary, this doctoral research study confirms the potential of plasma derived EVs as melanoma biomarkers, reveals their interaction with chemokines, and advocates for canine melanoma as a parallel research model. These findings could guide better strategies in melanoma treatment and outcomes, benefiting both human and canine health.

2026-02-03 JG: Hand signatures removed for GDPR compliance