(P 37) DISSECTING THE ROLE OF EXTRACELLULAR VESICLES IN THE MANAGEMENT OF GIST

Objective: Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal neoplasm of the gastrointestinal tract. Their biological and clinical behavior can vary from indolent to aggressive depending on different factors including the anatomic location, size and molecular profile. The limited availability of circulating biomarkers which could provide information about the aggressiveness of these rare tumors represents an urgent clinical need in order to guide physicians in the clinical management. Exosomes belong to the group of extracellular vesicles (EV) and play a key role in cellular functions and management of intercellular communication, thus representing a powerful tool for diagnostic applications and clinical settings. To this purpose, we analyzed physiochemical properties and genomic profile of exosomes in a case series of GIST and we correlated the results with the observed aggressiveness features of these malignancies.

Methods: Twenty-five patients affected by GIST were enrolled in the study. Blood sampling of each patients was performed intraoperatively and serum was obtained. Exosomes were isolated from blood serum and characterized by nanoparticle tracking analysis (NTA), dynamic light scattering (DLS) in terms of size, polydispersity, conductivity and zeta potentials, as well as surface antigen profiling using a 37 exosomal surface epitopes biomarkers MACSPlex Exosome Kit. To create a patient clustering, all gathered data were compared to the clinical history of the patients.

Results: The study included 17 GIST with a lesion smaller than 5 cm and 8 GIST greater than or equal to 5 cm. The risk of recurrence was classified as low in 18 patients while 7 patients exhibited an intermediate/high risk. The obtained data showed a no significant stratification for NTA and DLS, in contrast to the results of surface antigen profiling of vesicles analysis. The antigen profiling data showed that an increased expression of CD4 and CD209 antigens correlated significantly with an increased risk of recurrence, while an increased CD14 expression correlated with increased lesion size. A trend of significance was observed in the correlation between the up regulation of CD1c, ROR1, MCSP1 and CD86 and the increase of the risk of recurrence. Moreover, up regulation of HLA-DR, ROR1, CD86, CD14 was significantly associated with combined parameter of increased risk of recurrence and larger tumor size, whereas a trend of significance was observed with CD133/1.

Conclusion: These preliminary results suggest the promising use of circulating vesicles as a prognostic tool for the management of patients with GIST. Notably, we include evidence of the importance of surface antigen profiling of exosomes for patient stratification in terms of tumor aggressiveness and recurrence risk. Genomic analyses are currently underway to investigate the correlation between differentially expressed antigens and inflammatory signaling pathways associated with the presence of macrophages. Future investigation on a wider cohort including additional genomic analyses could better define the biological role of circulating exosomes as promising biomarkers for the management of GIST.