Yokoi Kazunori, Wang Jing, Yoshioka Yusuke, Fujisawa Yasuhiro, Fujimoto Manabu, Ochiya Takahiro, Tanemura Atsushi
Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
Acta Derm Venereol. 2025 Feb 25;105:adv40902. doi: 10.2340/actadv.v105.40902.
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.
皮肤血管肉瘤是一种罕见且侵袭性很强的皮肤恶性肿瘤。本研究旨在探索血管肉瘤患者血清来源的细胞外囊泡(EV)的变化,并评估其作为一种新型循环生物标志物的临床应用价值。在一项微阵列分析中,检测皮肤血管肉瘤患者与健康对照者血清中特定EV相关微小RNA的差异表达,结果在血管肉瘤患者中分别鉴定出73种显著上调和100种显著下调的微小RNA。其中,定量PCR证实,与健康对照者和黑色素瘤患者相比,皮肤血管肉瘤患者血清中的miR-184、miR-3925-5p、miR-3926和miR-5703上调。此外,与正常人内皮细胞系相比,这4种微小RNA在血管肉瘤细胞系中表达更高,并且随着疾病进展易于升高。此外,基因分析预测,微小RNA的靶基因集可能通过MECP2的表观遗传调控影响TP53的调节。综上所述,循环中的这4种细胞外囊泡相关微小RNA有望作为一种液体生物标志物来识别血管肉瘤患者并追踪疾病进展。