"Best Poster Award Authors Under 35" indetto dal Journal of Experimental & Clinical Cancer Research nel corso del "36th International AICC (Associazione Italiana Colture Cellulari) meeting".

Introduction Melanoma is the most aggressive skin cancer, with 50% of patients with metastatic or unresectable melanoma facing high 5-year mortality. Identifying non-invasive biomarkers for diagnosing and stratifying metastatic melanoma could prove essential to guide treatment decisions. MicroRNAs (miRNAs), small non-coding RNA molecules abundant in extracellular vesicles (EVs), have been studied as biomarkers in various cancers. This study aims to identify EV-miRNAs as circulating biomarkers in metastatic melanoma and assess their role in treatment response. Methods We explored EV-miRNAs in unresectable stage III and IV melanoma patients treated with immune checkpoint inhibitors (ICI) and Guadecitabine (NIBIT-M4 clinical trial). Plasma was collected before treatment (W0) and 12 weeks (W12) after treatment, and EVs were isolated for miRNA profiling. EV-miRNA profiling was first conducted on W0 samples and on a matched cohort of healthy donors. Enrichment analysis and logistic regression analysis were used to characterize differentially expressed (DE) EV-miRNAs at W0 and identify a specific signature distinguishing metastatic melanoma patients from healthy individuals. This signature was validated in an external publicly available dataset and in an independent internal cohort using droplet digital PCR, confirming its diagnostic relevance. Clinicians classified patients as responders (R) or non-responders (NR), and EV-miRNA profiles at W12 were analysed to be associated with treatment response. Results At W0, EV-miRNAs profiling found 65 DE EV-miRNAs distinguishing melanoma patients from healthy controls. The enrichment analysis performed on these DE EV-miRNAs showed their involvement in migration, angiogenesis, and immune regulation. Logistic regression analysis identified as a signature 4 EV-miRNAs (3 up-regulated: miR-412-3p, miR-507, miR-1203; 1 down-regulated: miR- 362-3p) distinguishing patients from healthy controls. At W12, 58 EV-miRNAs were modulated compared to W0, and two EV-miRNAs, including one from the diagnostic signature, were associated with treatment response. Conclusions These findings suggest that the two discovered EV-miRNAs could be useful as non-invasive biomarkers for monitoring response to ICI and Guadecitabine treatment, highlighting EV-miRNAs as a tool for precision medicine.