Novel Detection and Clinical Utility of Serum-Derived Extracellular Vesicle in Angiosarcoma

Cutaneous angiosarcoma is a rare and highly aggressive skin malignancy. The aim of this study is to explore the alteration of serum-derived extracellular vesicle (EV) in angiosarcoma patients and to evaluate its clinical utility as a novel circulating biomarker. In a microarray analysis to examine the differential expression of specific EV-associated microRNAs in sera between cutaneous angiosarcoma patients and healthy controls, 73 microRNAs with significant upregulation and 100 microRNAs with significant downregulation, respectively, were identified in patients with angio-sarcoma. Among them, quantitative PCR confirmed that miR-184, miR-3925-5p, miR-3926, and miR-5703 were upregulated in sera of cutaneous angiosarcoma patients compared with those of healthy controls and melanoma patients. Additionally, these 4 microRNAs were expressed more highly in angiosarcoma cell lines compared with normal human endothelial cell lines and were prone to elevate along with disease progression. Furthermore, a gene analysis predicted that the target gene set of microRNAs might affect the regulation of TP53 via the epigenetic regulation of MECP2. Taken together, these 4 extracellular vesicle-associated microRNAs in circulation serve as a promising liquid biomarker to identify angiosarcoma patients and trace disease progression.